The Experts below are selected from a list of 165 Experts worldwide ranked by ideXlab platform
Peter K.t. Pang - One of the best experts on this subject based on the ideXlab platform.
-
Quantitative determination of parathyroid Hypertensive Factor by enzyme-linked immunosorbent assay.
American journal of hypertension, 2000Co-Authors: Svetlana Krylova, Peter K.t. Pang, Richard Z. Lewanczuk, Jacqueline J. Shan, Christina G. BenishinAbstract:A new competitive enzyme immunoassay for the detection parathyroid Hypertensive Factor (PHF) in human plasma using a PHF-horseradish peroxidase conjugate and IgM antibody adsorbed on the microtiter plate was established. The antibodies raised against rat PHF could recognize human PHF. Cross-reactivity of anti-PHF antibodies with other serum haptens and proteins was negligible. Conjugation of PHF with horseradish peroxidase did not neutralize the antigen activity. The limit of detection of PHF was 0.02 U/mL in reference units and PHF levels between 0.02 and 1 U/mL could be detected. Within-run coefficient of variation (CV) was less than 10%, and between-run CV was less than 15% for over the dynamic range of the assay. Preliminary clinical studies were performed with plasma samples from Hypertensive patients with confirmed diagnosis. Parathyroid Hypertensive Factor levels, as detected with this immunoassay, were positively correlated with PHF levels detected with the semiquantitative blood pressure (BP) bioassay previously used. Parathyroid Hypertensive Factor levels detected with the enzyme-linked immunosorbent assay (ELISA) were also correlated with BP in patients. The PHF ELISA provides a selective, simple, and rapid method that can be used for routine determination of PHF in human plasma, and provides useful clinical information.
-
Parathyroid Hypertensive Factor secretion from subcultured spontaneously Hypertensive rat parathyroid cells.
American Journal of Hypertension, 1999Co-Authors: Christina G. Benishin, Jacqueline J. Shan, Richard Z. Lewanczuk, Peter K.t. PangAbstract:Cells dissociated from spontaneously Hypertensive rat (SHR) parathyroid glands were grown in culture. Media harvested from the cell cultures were analyzed for parathyroid Hypertensive Factor (PHF) using the blood pressure bioassay. Cells raised in DMEM containing normal (1.8 mmol/L) CaCl2 secreted a negligible amount of PHF, while cells cultured in Ham's F-12 medium containing low (0.3 mmol/L) CaCl2 secreted higher amounts of PHF. The PHF secretion in Ham's F-12 medium was highest in early passage cells, and was maintained for approximately 12 to 15 passages. PHF purified from the cell culture medium exhibited chromatographic properties identical to those previously described for PHF isolated from SHR plasma or SHR parathyroid gland organ culture medium. These results support the parathyroid gland as the organ of origin of PHF.
-
Clinical aspects of parathyroid Hypertensive Factor.
Journal of Cardiovascular Pharmacology, 1994Co-Authors: Richard Z. Lewanczuk, C G Benishin, Jie Shan, Peter K.t. PangAbstract:To determine the clinical significance of parathyroid Hypertensive Factor (PHF), physiological studies previously performed in animal models of hypertension were parallelled by human studies. These studies revealed that PHF-like activity is present in human hypertension, where it correlates with the salt-sensitive, low-renin state. As in spontaneously Hypertensive rats, both supplemental calcium and calcium-channel blockers appear to be useful in the treatment of PHF-related hypertension. In primary hyperparathyroid patients, PHF presence is linked with the presence of hypertension. Postparathyroidectomy blood pressure falls in parallel with PHF levels. These preliminary human studies suggest that PHF may be a useful marker in the treatment of hypertension.
-
PHF: The New Parathyroid Hypertensive Factor
Blood pressure, 1994Co-Authors: Peter K.t. Pang, Christina G. Benishin, Jie Shan, Richard Z. LewanczukAbstract:Parathyroid Hypertensive Factor (PHF) was discovered in SHR rats as a circulating substance with a unique delayed (60–90 min) Hypertensive effect when injected into a normotensive assay rat. Subsequently, this correlation with hypertension was established in humans, especially in low-renin, salt-sensitive patients. Animal model studies also confirmed this correlation. Endocrinectomy and glandular replacement studies suggested that the parathyroid gland was the source of PHF. Subsequently, glands and cells in culture were also shown to secrete the substance. Other studies verified the parathyroid origin of PHF. The mechanism of action of PHF was shown to rely mainly on the opening of L-type calcium channels in vascular smooth muscle cells with an increase in [Ca++]i It is known that diseases other than hypertension often show increased [Ca++]i and clinical features similar to hypertension, among them Type II diabetes. A recent study shows a correlation between circulating PHF level and Type II diabetes irr...
-
Effects of weight reduction on circulating parathyroid Hypertensive Factor levels.
Journal of Cardiovascular Pharmacology, 1994Co-Authors: James R. Sowers, R Z Lewanczuk, P. R. Standley, Peter K.t. PangAbstract:This study evaluated changes in parathyroid Hypertensive Factor (PHF) in 18 obese individuals. PHF levels were measured prior to the onset of a low calorie diet (800 kcal/day), and at 3-4 weeks, 7-8 weeks, and 11-12 weeks after initiation of the diet. Blood pressure, forearm vascular resistance, and platelet intracellular calcium ([Ca2+]i) levels were also measured at the same time. Although blood pressure, vascular resistance, and platelet [Ca2+]i decreased significantly in association with the low-calorie diet and weight reduction, PHF levels did not change significantly during the 12-week diet period. We conclude that PHF levels do not track with reductions in blood pressure, vascular resistance, and platelet [Ca2+]i levels in obese individuals.
Christina G. Benishin - One of the best experts on this subject based on the ideXlab platform.
-
Regulation of parathyroid Hypertensive Factor secretion by vitamin D3 analogs in parathyroid cells derived from spontaneously Hypertensive rats.
Journal of cellular biochemistry, 2005Co-Authors: Sharla K. Sutherland, Ilka Nemere, Christina G. BenishinAbstract:Parathyroid Hypertensive Factor (PHF) is a novel substance secreted by the parathyroid gland (PTG), which is elevated in 30-40% of all Hypertensive patients; specifically, the low-renin subset. However, very little is known about the regulation of PHF secretion. Since the classical parathyroid regulator, 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), may be elevated concurrent with or preceding the development of low-renin hypertension and elevated plasma PHF, we hypothesized that 1,25-(OH)2D3 would stimulate PHF release. To test this hypothesis, PTG organ and cell cultures, derived from spontaneously Hypertensive rats (SHR) and the normotensive genetic control Wistar Kyoto (WKY) rats, were exposed to various vitamin D3 metabolites and PHF release measured by ELISA. 1,25-(OH)2D3 rapidly stimulated PHF release with enhanced sensitivity in SHR versus WKY cultures indicated by a leftward shift in the dose-response curve, whereas 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) had the converse effect. Vitamin D3 analog ''BT,'' an agonist for the classical nuclear vitamin D receptor (1,25VDRnuc), was without effect suggesting a 1,25VDRnuc-independent mechanism and potential involvement of the plasma membrane-bound vitamin D receptor (1,25 D3-MARRS). Interestingly, protein expression of the 1,25 D3-MARRS was increased in SHR versus WKY parathyroid cells. In conclusion, these results support the idea that 1,25-(OH)2D3 may contribute to elevated plasma PHF in the SHR. J. Cell. Biochem. 96: 97-108, 2005. 2005 Wiley-Liss, Inc.
-
Regulation of parathyroid Hypertensive Factor secretion by Ca2+ in spontaneously Hypertensive rat parathyroid cells
American journal of hypertension, 2004Co-Authors: Sharla K. Sutherland, Christina G. BenishinAbstract:Abstract Background Elevated parathyroid Hypertensive Factor (PHF) has been suggested to play a causal role in the pathogenesis of hypertension. Previous studies have indicated that PHF secretion is stimulated by low extracellular (EC) Ca2+. Therefore, we hypothesized that the calcium-sensing receptor (CaR) is involved in regulation of PHF release. Methods Parathyroid gland (PTG) organ and cell cultures derived from spontaneously Hypertensive rats (SHR) or Wistar-Kyoto (WKY) rats were exposed to low and normal EC Ca2+ and PHF release measured by ELISA. Expression of CaR protein was assessed by Western blot. Results Low EC Ca2+ stimulated both SHR and WKY PTG organ cultures to secrete more PHF, first observable after 60 min incubation. After 4 h, PHF secretion was stimulated (66-fold v 24-fold stimulation for SHR and WKY, respectively). Cultured SHR and WKY parathyroid cells were also stimulated, but to a lesser extent (2.63-fold v 3.75-fold stimulation for SHR and WKY respectively). After 24 h the stimulation by low EC Ca2+ was no longer apparent. Expression of CaR is elevated in the SHR relative to WKY PTG. In both strains expression is higher under conditions of normal (1.5 mmol/L) EC Ca2+ and it increases with incubation time. The apparent suppression of PHF release by normal (1.5 mmol/L) EC Ca2+ is blocked by pre-exposure of the PTG cells to anti-CaR antibody. Conclusions Low EC Ca2+ stimulated rapid PHF release from both SHR and WKY PTG. Changes in CaR expression may account for different sensitivity to EC Ca2+ of the two strains and over time.
-
Generation, Characterization, and Use of Monoclonal Antibodies against Parathyroid Hypertensive Factor
Clinical chemistry, 2003Co-Authors: Svetlana Krylova, Richard Z. Lewanczuk, Teresa Labedz, Christina G. BenishinAbstract:Parathyroid Hypertensive Factor (PHF) may be useful as a diagnostic marker of salt-sensitive, low-renin hypertension. PHF was discovered in the plasma of salt-sensitive Hypertensive humans (1) and was also found to be increased in spontaneously Hypertensive rats, DOCA-salt-Hypertensive rats, and Dahl-salt-sensitive rats, but not in two-kidney one-clip rats or in Dahl-salt-insensitive rats (2)(3). Studies on the mechanism of PHF action indicate that this substance acts directly on vascular smooth muscle cells to enhance Ca2+ influx (4), likely associated with depolarization of the plasma membrane by inhibition of voltage-gated K+ channels (5). Together these actions will sensitize vascular tissues to other vasoconstrictors, such as norepinephrine and angiotensin II (6). PHF may therefore be a causative Factor in the development of hypertension in some individuals. It was found that PHF-positive (salt-sensitive) patients respond best to calcium channel blockers and diuretics and that PHF-negative patients respond better to angiotensin-converting enzyme inhibitors and beta blockers (7). Recently, an enzyme immunoassay for detection of PHF in human plasma has been reported that uses anti-PHF oligoclonal antibodies (8). The present study describes the further development, characterization, and clinical application of monoclonal antibodies (MAbs) against PHF. Male BALB/c mice were immunized with partially purified PHF (9) prepared from medium harvested from cultured parathyroid glands of spontaneously Hypertensive rats, as was described previously (10). Splenocytes were harvested and fused with SP/0-2 myeloma cells by standard procedures (11). The recloning procedure involved limiting-dilution conditions in 96-well plates (0.3 cells/well). The bovine serum albumin (BSA) conjugate of PHF was synthesized by standard procedures (12) and used in a direct ELISA for anti-PHF antibodies. Microtiter plates were coated with BSA-PHF (100 μL/well; 1:2000 dilution). After the plates were washed with phosphate-buffered saline (PBS) containing 5 mL/L Tween 20, supernatants of hybridoma cell cultures were added (100 μL/well) and …
-
Quantitative determination of parathyroid Hypertensive Factor by enzyme-linked immunosorbent assay.
American journal of hypertension, 2000Co-Authors: Svetlana Krylova, Peter K.t. Pang, Richard Z. Lewanczuk, Jacqueline J. Shan, Christina G. BenishinAbstract:A new competitive enzyme immunoassay for the detection parathyroid Hypertensive Factor (PHF) in human plasma using a PHF-horseradish peroxidase conjugate and IgM antibody adsorbed on the microtiter plate was established. The antibodies raised against rat PHF could recognize human PHF. Cross-reactivity of anti-PHF antibodies with other serum haptens and proteins was negligible. Conjugation of PHF with horseradish peroxidase did not neutralize the antigen activity. The limit of detection of PHF was 0.02 U/mL in reference units and PHF levels between 0.02 and 1 U/mL could be detected. Within-run coefficient of variation (CV) was less than 10%, and between-run CV was less than 15% for over the dynamic range of the assay. Preliminary clinical studies were performed with plasma samples from Hypertensive patients with confirmed diagnosis. Parathyroid Hypertensive Factor levels, as detected with this immunoassay, were positively correlated with PHF levels detected with the semiquantitative blood pressure (BP) bioassay previously used. Parathyroid Hypertensive Factor levels detected with the enzyme-linked immunosorbent assay (ELISA) were also correlated with BP in patients. The PHF ELISA provides a selective, simple, and rapid method that can be used for routine determination of PHF in human plasma, and provides useful clinical information.
-
Parathyroid Hypertensive Factor inhibits voltage- gated K + channels in vascular smooth muscle cells
Canadian journal of physiology and pharmacology, 1999Co-Authors: Jun Ren, Lei Zhang, Christina G. BenishinAbstract:Parathyroid Hypertensive Factor (PHF) has been implicated in regulation of vascular smooth muscle tone and pathogenesis of several forms of hypertension. Earlier studies have suggested that PHF enhances the actions of other vasoconstrictors, while it has no in vitro vasoconstrictor property of its own. PHF was previously found to enhance the L-type Ca channel currents and intracellular Ca responses to depolarization in vascular smooth muscle cells (VSMCs). The present study examined whether PHF might act on K channels in the plasma membrane of VSMCs. Primary cultured VSMCs from rat tail artery were used. The whole-cell version of the patch-clamp technique was used under conditions in which there was no contribution of Ca-activated K channels to the outward current. Both purified and semipurified PHF inhibited the delayed rectifier type potassium current in a dose-dependent manner. The effect was time dependent and was first significantly different from the control current after 30 min. The inhibition of the delayed rectifier K channel was associated with a time-dependent decrease in the resting membrane potential. Therefore, PHF may alter VSMC cellular Ca responses by reducing the membrane potential to a level closer to the activation potential of Ca channels. Resume : Le facteur hypertensif des parathyroides (FHP) a ete mis en cause dans la regulation du tonus du muscle lisse vasculaire et dans la pathogenese de plusieurs formes d'hypertension. Des etudes anterieures ont semble indiquer que le FHP stimule les actions d'autres vasoconstricteurs, alors qu'il n'a aucune propriete vasoconstrictrice particuliere in vitro. Des etudes ont deja montre que le FHP stimule les courants des canaux Ca de type L ainsi que les reponses du Ca intracellulaire a une depolarisation dans les cellules du muscle lisse vasculaire (CMLV). La presente etude a eu pour but d'examiner si le FHP peut agir sur les canaux K dans la membrane plasmatique des CMLV. Pour ce faire, on a utilise des CMLV d'artere caudale de rats en culture primaire. La technique du patch clamp de la cellule entiere a ete utilisee dans des conditions ou les canaux K actives par le Ca ne contribuent pas au courant sortant. Le FHP tant purifie que semi-purifie a inhibe de maniere concentration dependante le courant de potassium a redressement retarde. L'effet a ete fonction du temps et differait significativement du courant temoin apres 30 min. L'inhibition du courant K a redressement retarde a ete associee a une diminution dependante du temps du potentiel membranaire au repos. Ainsi, le FHP pourrait modifier les reponses du Ca cellulaire des CMLV en reduisant le potentiel membranaire a un taux se rapprochant du potentiel d'activation des canaux Ca. Mots cles : facteur hypertensif des parathyroides, hypertension, canaux de potassium, muscle lisse vasculaire, potentiel membranaire.
Richard Z. Lewanczuk - One of the best experts on this subject based on the ideXlab platform.
-
Generation, Characterization, and Use of Monoclonal Antibodies against Parathyroid Hypertensive Factor
Clinical chemistry, 2003Co-Authors: Svetlana Krylova, Richard Z. Lewanczuk, Teresa Labedz, Christina G. BenishinAbstract:Parathyroid Hypertensive Factor (PHF) may be useful as a diagnostic marker of salt-sensitive, low-renin hypertension. PHF was discovered in the plasma of salt-sensitive Hypertensive humans (1) and was also found to be increased in spontaneously Hypertensive rats, DOCA-salt-Hypertensive rats, and Dahl-salt-sensitive rats, but not in two-kidney one-clip rats or in Dahl-salt-insensitive rats (2)(3). Studies on the mechanism of PHF action indicate that this substance acts directly on vascular smooth muscle cells to enhance Ca2+ influx (4), likely associated with depolarization of the plasma membrane by inhibition of voltage-gated K+ channels (5). Together these actions will sensitize vascular tissues to other vasoconstrictors, such as norepinephrine and angiotensin II (6). PHF may therefore be a causative Factor in the development of hypertension in some individuals. It was found that PHF-positive (salt-sensitive) patients respond best to calcium channel blockers and diuretics and that PHF-negative patients respond better to angiotensin-converting enzyme inhibitors and beta blockers (7). Recently, an enzyme immunoassay for detection of PHF in human plasma has been reported that uses anti-PHF oligoclonal antibodies (8). The present study describes the further development, characterization, and clinical application of monoclonal antibodies (MAbs) against PHF. Male BALB/c mice were immunized with partially purified PHF (9) prepared from medium harvested from cultured parathyroid glands of spontaneously Hypertensive rats, as was described previously (10). Splenocytes were harvested and fused with SP/0-2 myeloma cells by standard procedures (11). The recloning procedure involved limiting-dilution conditions in 96-well plates (0.3 cells/well). The bovine serum albumin (BSA) conjugate of PHF was synthesized by standard procedures (12) and used in a direct ELISA for anti-PHF antibodies. Microtiter plates were coated with BSA-PHF (100 μL/well; 1:2000 dilution). After the plates were washed with phosphate-buffered saline (PBS) containing 5 mL/L Tween 20, supernatants of hybridoma cell cultures were added (100 μL/well) and …
-
Quantitative determination of parathyroid Hypertensive Factor by enzyme-linked immunosorbent assay.
American journal of hypertension, 2000Co-Authors: Svetlana Krylova, Peter K.t. Pang, Richard Z. Lewanczuk, Jacqueline J. Shan, Christina G. BenishinAbstract:A new competitive enzyme immunoassay for the detection parathyroid Hypertensive Factor (PHF) in human plasma using a PHF-horseradish peroxidase conjugate and IgM antibody adsorbed on the microtiter plate was established. The antibodies raised against rat PHF could recognize human PHF. Cross-reactivity of anti-PHF antibodies with other serum haptens and proteins was negligible. Conjugation of PHF with horseradish peroxidase did not neutralize the antigen activity. The limit of detection of PHF was 0.02 U/mL in reference units and PHF levels between 0.02 and 1 U/mL could be detected. Within-run coefficient of variation (CV) was less than 10%, and between-run CV was less than 15% for over the dynamic range of the assay. Preliminary clinical studies were performed with plasma samples from Hypertensive patients with confirmed diagnosis. Parathyroid Hypertensive Factor levels, as detected with this immunoassay, were positively correlated with PHF levels detected with the semiquantitative blood pressure (BP) bioassay previously used. Parathyroid Hypertensive Factor levels detected with the enzyme-linked immunosorbent assay (ELISA) were also correlated with BP in patients. The PHF ELISA provides a selective, simple, and rapid method that can be used for routine determination of PHF in human plasma, and provides useful clinical information.
-
Parathyroid Hypertensive Factor secretion from subcultured spontaneously Hypertensive rat parathyroid cells.
American Journal of Hypertension, 1999Co-Authors: Christina G. Benishin, Jacqueline J. Shan, Richard Z. Lewanczuk, Peter K.t. PangAbstract:Cells dissociated from spontaneously Hypertensive rat (SHR) parathyroid glands were grown in culture. Media harvested from the cell cultures were analyzed for parathyroid Hypertensive Factor (PHF) using the blood pressure bioassay. Cells raised in DMEM containing normal (1.8 mmol/L) CaCl2 secreted a negligible amount of PHF, while cells cultured in Ham's F-12 medium containing low (0.3 mmol/L) CaCl2 secreted higher amounts of PHF. The PHF secretion in Ham's F-12 medium was highest in early passage cells, and was maintained for approximately 12 to 15 passages. PHF purified from the cell culture medium exhibited chromatographic properties identical to those previously described for PHF isolated from SHR plasma or SHR parathyroid gland organ culture medium. These results support the parathyroid gland as the organ of origin of PHF.
-
Parathyroid Hypertensive Factor Predicts Efficacy in the Treatment of Essential Hypertension with Verapamil
Blood pressure, 1996Co-Authors: Richard Z. Lewanczuk, Peter G. HamiltonAbstract:Lewanczuk RZ, Hamilton PC. Parathyroid Hypertensive Factor predicts efficacy in the treatment of essential hypertension with verapamil.Parathyroid Hypertensive Factor (PHF) is a circulating Hypertensive Factor, levels of which are inversely related to renin profile. Given this relationship, it was hypothesized that a PHF level might serve as an alternate predictor of antiHypertensive efficacy in Hypertensive patients, avoiding the difficulties associated with renin profiling. To test this hypothesis, thirty patients with essential hypertension were placed on 240 mg once daily of a slow release verapamil preparation for a period of one month following a one month run-in period. Results showed an average reduction in mean arterial pressure (MAP) of -7mmHg (range -5 to -18) and an average reduction in PHF of -4mmHg (range 7 to -28). Pre-treatment PHF level correlated with the blood pressure response to verapamil (r = -0.61, p =0.0004). There was no correlation between any index of renin status and blood pres...
-
PHF: The New Parathyroid Hypertensive Factor
Blood pressure, 1994Co-Authors: Peter K.t. Pang, Christina G. Benishin, Jie Shan, Richard Z. LewanczukAbstract:Parathyroid Hypertensive Factor (PHF) was discovered in SHR rats as a circulating substance with a unique delayed (60–90 min) Hypertensive effect when injected into a normotensive assay rat. Subsequently, this correlation with hypertension was established in humans, especially in low-renin, salt-sensitive patients. Animal model studies also confirmed this correlation. Endocrinectomy and glandular replacement studies suggested that the parathyroid gland was the source of PHF. Subsequently, glands and cells in culture were also shown to secrete the substance. Other studies verified the parathyroid origin of PHF. The mechanism of action of PHF was shown to rely mainly on the opening of L-type calcium channels in vascular smooth muscle cells with an increase in [Ca++]i It is known that diseases other than hypertension often show increased [Ca++]i and clinical features similar to hypertension, among them Type II diabetes. A recent study shows a correlation between circulating PHF level and Type II diabetes irr...
Jie Shan - One of the best experts on this subject based on the ideXlab platform.
-
Clinical aspects of parathyroid Hypertensive Factor.
Journal of Cardiovascular Pharmacology, 1994Co-Authors: Richard Z. Lewanczuk, C G Benishin, Jie Shan, Peter K.t. PangAbstract:To determine the clinical significance of parathyroid Hypertensive Factor (PHF), physiological studies previously performed in animal models of hypertension were parallelled by human studies. These studies revealed that PHF-like activity is present in human hypertension, where it correlates with the salt-sensitive, low-renin state. As in spontaneously Hypertensive rats, both supplemental calcium and calcium-channel blockers appear to be useful in the treatment of PHF-related hypertension. In primary hyperparathyroid patients, PHF presence is linked with the presence of hypertension. Postparathyroidectomy blood pressure falls in parallel with PHF levels. These preliminary human studies suggest that PHF may be a useful marker in the treatment of hypertension.
-
Purification and structural characterization of parathyroid Hypertensive Factor.
Journal of cardiovascular pharmacology, 1994Co-Authors: C G Benishin, Jie Shan, R Z Lewanczuk, P K PangAbstract:Parathyroid Hypertensive Factor (PHF) has been purified from two sources of material: plasma of spontaneously Hypertensive rats (SHRs) and culture medium from organ culture of SHR parathyroid glands. Chromatographic characteristics of PHF from these two sources are identical. Biological activity of PHF (assayed as the characteristic delayed Hypertensive response in normotensive rats) is sensitive to degradation by treatment in base, and the enzymes trypsin, chymotrypsin, phospholipase C, and phospholipase D. PHF activity may also be extracted from source material with chloroform: methanol (4:1). A hypothetical structure for the active component of PHF is suggested. This is comprised of a peptide liked to a lysophospholipid.
-
PHF: The New Parathyroid Hypertensive Factor
Blood pressure, 1994Co-Authors: Peter K.t. Pang, Christina G. Benishin, Jie Shan, Richard Z. LewanczukAbstract:Parathyroid Hypertensive Factor (PHF) was discovered in SHR rats as a circulating substance with a unique delayed (60–90 min) Hypertensive effect when injected into a normotensive assay rat. Subsequently, this correlation with hypertension was established in humans, especially in low-renin, salt-sensitive patients. Animal model studies also confirmed this correlation. Endocrinectomy and glandular replacement studies suggested that the parathyroid gland was the source of PHF. Subsequently, glands and cells in culture were also shown to secrete the substance. Other studies verified the parathyroid origin of PHF. The mechanism of action of PHF was shown to rely mainly on the opening of L-type calcium channels in vascular smooth muscle cells with an increase in [Ca++]i It is known that diseases other than hypertension often show increased [Ca++]i and clinical features similar to hypertension, among them Type II diabetes. A recent study shows a correlation between circulating PHF level and Type II diabetes irr...
-
Clinical aspects of parathyroid Hypertensive Factor.
Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1994Co-Authors: Richard Z. Lewanczuk, Christina G. Benishin, Jie Shan, Lawrence M. Resnick, Peter K.t. PangAbstract:Parathyroid Hypertensive Factor (PHF) in rats: PHF is an endogenous Hypertensive substance which was originally associated with hypertension in spontaneously Hypertensive rats (SHR). In this model, PHF was shown to act by increasing intracellular calcium levels in vascular smooth muscle and was linked with a characteristic pattern of abnormalities in overall calcium regulation. The action of PHF was blocked by calcium antagonists, suggesting that the effect of PHF was to increase extracellular calcium uptake. In SHR the parathyroid glands were shown to be the site of PHF secretion. This secretion was inhibited by an increase in dietary calcium. PHF was further shown to be unique to low-renin forms of hypertension, that is, those forms of hypertension characterized by abnormalities in calcium metabolism. PHF in humans: PHF was subsequently found in human low-renin salt-sensitive hypertension. As in SHR, calcium supplementation can lower PHF levels in humans. Similarly, there is circumstantial evidence for the parathyroid origin of PHF in humans. In human Hypertensive patients, the presence of PHF has been shown to predict a favorable therapeutic response to calcium channel blockade. Recently, many of the abnormalities in calcium metabolism present in low-renin hypertension have also been described in other disease states. Notable among these diseases is non-insulin dependent diabetes mellitus. A survey of human non-insulin dependent diabetes mellitus has revealed that PHF was present in a disproportionate number of these patients independently of the blood pressure level. The significance of this latter finding needs to be explored, but PHF may prove to have relevance in diseases other than hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Mechanism of the vascular action of parathyroid Hypertensive Factor.
Journal of Cardiovascular Pharmacology, 1994Co-Authors: Jie Shan, Christina G. Benishin, Richard Z. Lewanczuk, Peter K.t. PangAbstract:The present studies investigated the effect of parathyroid Hypertensive Factor (PHF) on intracellular calcium regulation in VSMC. Nifedipine inhibited the Hypertensive effect of PHF in Sprague-Dawley (SD) rats in vivo. PHF amplified the L-type calcium current in vascular smooth-muscle cells (VSMCs) isolated from SD rat tail artery. PHF potentiated the tension induced by norepinephrine (NE) in the presence of normal added CaCl2 and inhibited the tension dependent on Ca2+ release from intracellular calcium store(s) induced by NE in SD rat tail artery helical strips. PHF potentiated the intracellular free calcium concentration ([Ca2+]i) increment induced by KCl in cultured VSMCs from SD rat tail artery. All of the in vitro cellular calcium effects of PHF temporally correlated with its delayed Hypertensive effect in vivo. PHF did not affect the accumulation of inositol phosphates in SD rat tail artery. Infusion of theophylline blunted the Hypertensive effect of PHF in SD rats, suggesting that PHF may stimulate phosphodiesterase (PDE) activity. We suggest that PHF may potentiate the effects of other vasoconstrictors on calcium channels and increase [Ca2+]i, which would then lead to an increase in the responsiveness of the VSMC to other vasoconstrictors, and therefore an increase in blood pressure. The action of PHF may involve stimulation of PDE activity.
Lawrence M. Resnick - One of the best experts on this subject based on the ideXlab platform.
-
Calciotropic hormones in salt-sensitive essential hypertension: 1,25-dihydroxyvitamin D and parathyroid Hypertensive Factor.
Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1994Co-Authors: Lawrence M. ResnickAbstract:Hypothesis Some, but not all, men and women display a pressor response to increases in dietary salt intake. The mechanism(s) underlying this salt-sensitive hypertension remains poorly defined. We have developed a hypothesis that all hypertension arises from an imbalance between mechanisms of cytosolic calcium accumulation from the extracellular space versus calcium release into the cytoplasm from intracellular storage sites. Extracellular calcium-dependent hypertension predominates in salt-sensitive subjects, while excess angiotensin II mediates the excess intracellular calcium release that is characteristic of renin-dependent salt-insensitive forms of hypertension. Studies on pressor hormones: We investigated potential etiologic Factors mediating the cellular calcium accumulation in salt-sensitive Hypertensive human subjects, and focused on two calcium-related circulating hormonal substances, 1,25-dihydroxyvitamin D and the recently described parathyroid Hypertensive Factor. Both of these substances directly facilitate calcium transport from the extracellular space in the cell. Furthermore, levels of these hormones are greatest in black normotensive and low-renin essential Hypertensive subjects, both groups associated with salt-related Hypertensive disease. Lastly, dietary salt loading elevates 1,25-dihydroxyvitamin D and parathyroid Hypertensive Factor levels, and the greater the level of either hormone, the greater the pressor response to salt. Conclusions It is reasonable to consider that these salt-induced cellular ionophoric actions of 1,25-dihydroxyvitamin D and parathyroid Hypertensive Factor contribute, at least in part, to the mechanism of salt-sensitive hypertension in man.
-
Clinical aspects of parathyroid Hypertensive Factor.
Journal of hypertension. Supplement : official journal of the International Society of Hypertension, 1994Co-Authors: Richard Z. Lewanczuk, Christina G. Benishin, Jie Shan, Lawrence M. Resnick, Peter K.t. PangAbstract:Parathyroid Hypertensive Factor (PHF) in rats: PHF is an endogenous Hypertensive substance which was originally associated with hypertension in spontaneously Hypertensive rats (SHR). In this model, PHF was shown to act by increasing intracellular calcium levels in vascular smooth muscle and was linked with a characteristic pattern of abnormalities in overall calcium regulation. The action of PHF was blocked by calcium antagonists, suggesting that the effect of PHF was to increase extracellular calcium uptake. In SHR the parathyroid glands were shown to be the site of PHF secretion. This secretion was inhibited by an increase in dietary calcium. PHF was further shown to be unique to low-renin forms of hypertension, that is, those forms of hypertension characterized by abnormalities in calcium metabolism. PHF in humans: PHF was subsequently found in human low-renin salt-sensitive hypertension. As in SHR, calcium supplementation can lower PHF levels in humans. Similarly, there is circumstantial evidence for the parathyroid origin of PHF in humans. In human Hypertensive patients, the presence of PHF has been shown to predict a favorable therapeutic response to calcium channel blockade. Recently, many of the abnormalities in calcium metabolism present in low-renin hypertension have also been described in other disease states. Notable among these diseases is non-insulin dependent diabetes mellitus. A survey of human non-insulin dependent diabetes mellitus has revealed that PHF was present in a disproportionate number of these patients independently of the blood pressure level. The significance of this latter finding needs to be explored, but PHF may prove to have relevance in diseases other than hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)
-
Serum-mediated intracellular calcium changes in normotensive and Hypertensive red blood cells: role of parathyroid Hypertensive Factor.
Journal of Cardiovascular Pharmacology, 1994Co-Authors: Mario Barbagallo, Peter K.t. Pang, Richard Z. Lewanczuk, R. K. Gupta, Lawrence M. ResnickAbstract:To study cellular calcium metabolism in hypertension, we investigated the effects of human serum, and of the circulating pressor substance, parathyroid Hypertensive Factor (PHF), on the cytosolic free calcium (Cai-f) content of erythrocytes from normotensive and essential Hypertensive subjects. In their own serum, basal Cai-f was higher in Hypertensive than in normotensive and essential Hypertensive subjects. In their own serum, basal Cai-f was higher in Hypertensive than in normotensive subjects (mean +/- SEM; 39.4 +/- 4.0 vs. 23.4 +/- 2.7 nM; p < 0.05). Without serum, Cai-f was lower and not significantly different (23.0 +/- 3.1 vs. 18.2 +/- 2.7 nM; p = not significant). Addition of serum to serum-free erythrocytes increased Cai-f, and reestablished the Cai-f gradient in Hypertensive cells (31.4 +/- 0.8 vs 23.0 +/- 2.3 nM; p < 0.05). PHF levels were directly related to basal Cai-f (r = -0.648; p < 0.05) and to the serum-induced rise in Cai-f (r = 0.600; p < 0.05). Furthermore, semipurified PHF, but not similarly prepared normotensive serum, increased Cai-f in normal human erythrocytes (PHF: +83.9 +/- 37.3% vs. +14.5 +/- 27.5%; p < 0.05). We conclude that circulating Factors in general, and PHF in particular, may account for the increased basal Cai-f of hypertension, and thus at least partially contribute to te pathophysiology of the Hypertensive process.
-
Parathyroid Hypertensive Factor-like activity in human essential hypertension: relationship to plasma renin activity and dietary salt sensitivity.
Journal of hypertension, 1993Co-Authors: Lawrence M. Resnick, Richard Z. Lewanczuk, John H. Laragh, Peter K.t. PangAbstract:Objective: To determine the clinical relevance of the newly described circulating pressor Factor with parathyroid Hypertensive Factor (PHF)-like activity. Design: Plasma samples were collected from 94 normotensive and 93 essential Hypertensive subjects, the latter either previously defined by dietary salt sensitivity (n=43), or prospectively studied on both low- ( 200 mmol/day) diets (n=16). Methods: Blood pressure, demographic Factors, plasma renin activity (PRA), urinary electrolyte excretion and bioassayable PHF-like activity were determined in the fasted state on basal and altered dietary salt intakes