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Yasutaka Kurata - One of the best experts on this subject based on the ideXlab platform.
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exercise training attenuates anaphylactic Venoconstriction in rat perfused liver but does not affect anaphylactic hypotension in conscious rats
Clinical and Experimental Pharmacology and Physiology, 2010Co-Authors: Toshishige Shibamoto, Yasutaka Kurata, Wei Zhang, Osamu Kashimura, Shunichi MiyamaeAbstract:Summary 1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic Venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental Venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the Venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (Ppv) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (Rpre and Rpost, respectively). In conscious rats, systemic arterial pressure (SAP) and Ppv were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in Rpre and Rpost, respectively. The anaphylaxis-induced increase in Rpre was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with NG-nitro-l-arginine methyl ester (100 μmol/L) 10 min prior to the injection of antigen enhanced anaphylactic Venoconstriction, but did not alter the effect of exercise training on the increase in Rpre. In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.
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leukotrienes and cyclooxygenase products mediate anaphylactic Venoconstriction in ovalbumin sensitized rat livers
European Journal of Pharmacology, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Wei Zhang, Yasutaka KurataAbstract:Hepatic anaphylactic Venoconstriction is partly involved in anaphylactic hypotension. We determined the chemical mediators responsible for anaphylaxis-induced segmental Venoconstriction in perfused livers isolated from ovalbumin-sensitized rats. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The portal venous pressure (Ppv), hepatic venous pressure (Phv), liver weight and hepatic oxygen consumption were continuously measured. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. After antigen injection, both Ppv and Pdo increased, resulting in 5.6- and 1.6-fold increases in Rpre and Rpost, respectively. Liver weight showed a biphasic change of an initial decrease followed by an increase. Hepatic oxygen consumption significantly decreased after antigen. Anaphylaxis-induced increase in Rpre was most extensively inhibited by 38.6% by pretreatment with ONO-1078 (100 μM, a cysteinyl leukotriene receptor-1 antagonist), among all antagonists or inhibitors administrated individually including TCV-309 (20 μM), AA-2414 (10 μM), ketanserin (10 μM) and indomethacin (10 μM). Combined pretreatment with indomethacin and ONO-1078 exerted additive inhibitory effects and attenuated Rpre by 65.8%. However, TCV-309, a platelet activating factor (PAF) receptor antagonist, did not affect the anaphylactic response. In contrast, anaphylaxis-induced increase in Rpost was attenuated only by ONO-1078 combined pretreatment. The antigen-induced changes in liver weight and hepatic oxygen consumption were attenuated significantly when hepatic Venoconstriction was attenuated. It is concluded that cysteinyl leukotrienes and cyclooxygenase products, but not PAF, are mainly involved in anaphylaxis-induced pre-sinusoidal constriction in isolated perfused rat livers.
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effects of l name on thromboxane a2 induced Venoconstriction in isolated perfused livers from rat guinea pig and mouse
Vascular Pharmacology, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Zhansheng Zhao, Wei Zhang, Yasutaka KurataAbstract:Abstract Effects of l -NAME on U-46619 (a thromboxane A 2 , analogue) -induced hepatic segmental Venoconstriction were examined in mouse, rat and guinea pig isolated perfused livers. All livers were perfused portally and recirculatingly at a constant flow with diluted blood. U-46619 was administrated into the reservoir in a cumulative manner to gain the concentrations of 0.001–3 μM at 10 min after l -NAME or d -NAME (100 μM). The portal venous pressure, hepatic venous pressure and perfusate flow were monitored. In addition, the sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. U-46619 concentration-dependently caused predominant presinusoidal constriction in all three species. The rat livers were the strongest while the mouse livers were the weakest in responsiveness and sensitivity to U-46619. l -NAME mainly augmented the U-46619-induced increases in Rpre, but not in Rpost, in rat and guinea pig. This augmentation was stronger in rat. However, l -NAME did not augment the response to U-46619 in mouse. In conclusion, in rat and guinea pig, NO may be released selectively from the presinusoids in response to U-46619, and then attenuate the U-46619-induced presinusoidal constriction. In mouse, U-46619-induced Venoconstriction is weak and not modulated by NO.
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l name augments paf induced Venoconstriction in isolated perfused livers of rat and guinea pig but not mouse
Prostaglandins Leukotrienes and Essential Fatty Acids, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Zhansheng Zhao, Yasutaka KurataAbstract:Abstract Platelet-activating factor (PAF), one of vasoconstrictive lipid mediators, is involved in systemic anaphylaxis. On the other hand, nitric oxide (NO) is known to attenuate anaphylactic Venoconstriction of the pre-sinusoids in isolated guinea pig and rat livers. However, it is not known whether NO attenuates PAF-induced hepatic Venoconstriction. We therefore determined the effects of l -NAME, a NO synthase inhibitor, on PAF-induced Venoconstriction in blood- and constant flow-perfused isolated livers of mice, rats and guinea pigs. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. PAF (0.01–1 μM) concentration-dependently caused predominant pre-sinusoidal constriction in all livers of three species studied. The guinea pig livers were the most sensitive to PAF, while the mouse livers were the weakest in responsiveness. l -NAME pretreatment selectively increased the basal Rpre in all of three species. l -NAME also significantly augmented the PAF-induced increases in Rpre, but not in Rpost, in rat and guinea pig livers. This augmentation was stronger in rat livers than in guinea pig livers at the high concentration of 0.1 μM PAF. However, l -NAME did not augment PAF-induced Venoconstriction in mouse livers. In conclusion, in rat and guinea pig livers, NO may be released selectively from the pre-sinusoids in response to PAF, and then attenuate the PAF-induced pre-sinusoidal constriction. In mouse liver, PAF-induced Venoconstriction is weak and not modulated by NO.
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ng nitro l arginine methyl ester potentiates anaphylactic Venoconstriction in rat perfused livers
Clinical and Experimental Pharmacology and Physiology, 2006Co-Authors: Toshishige Shibamoto, Takaharu Ishibashi, Tomohiro Shimo, Hiromichi Takano, Hideaki Tsuchida, Matomo Nishio, Yasutaka KurataAbstract:1. The effects of the nitric oxide (NO) synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on anaphylaxisinduced Venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic Venoconstriction. 2. Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs'-Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with L-NAME (100 μmol/L) or D-NAME (100 μmol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO (NO - 2 and NO - 3 ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen caused hepatic Venoconstriction, as evidenced by an increase in Ppv from a mean (±SEM) baseline value of 7.7 ± 0.1 cmH 2 O to a peak of 21.4 ± 1.1 cmH 2 O at 3 min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic Venoconstriction, as reflected by a higher Ppv (27.4 ± 0.8 cmH 2 O) after antigen than observed following D-NAME pretreatment. The addition of L-arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic Venoconstriction. However, perfusate NO x levels did not increase significantly after antigen in livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME potentiates rat anaphylactic hepatic Venoconstriction, suggesting that NO contributes to the attenuation of the Venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NO x concentrations.
Toshishige Shibamoto - One of the best experts on this subject based on the ideXlab platform.
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exercise training attenuates anaphylactic Venoconstriction in rat perfused liver but does not affect anaphylactic hypotension in conscious rats
Clinical and Experimental Pharmacology and Physiology, 2010Co-Authors: Toshishige Shibamoto, Yasutaka Kurata, Wei Zhang, Osamu Kashimura, Shunichi MiyamaeAbstract:Summary 1. Exercise training attenuates circulatory shock due to haemorrhage, endotoxin or heatstroke. However, it remains unknown whether exercise training attenuates anaphylactic shock. Hepatic Venoconstriction is involved in rat anaphylactic hypotension. In the present study, we determined the effects of exercise training on both anaphylaxis-induced segmental Venoconstriction in rat perfused livers and systemic anaphylaxis in conscious rats. The role of nitric oxide (NO) in the effect of exercise on the Venoconstriction of perfused livers was also examined. 2. Rats were subjected to running training on a motorized treadmill for 4 weeks. Two weeks prior to the anaphylaxis experiment, Sprague-Dawley rats were actively sensitized with the antigen ovalbumin. In isolated livers perfused portally with blood, the portal venous pressure (Ppv) and sinusoidal pressure were measured to determine the pre- and post-sinusoidal resistances (Rpre and Rpost, respectively). In conscious rats, systemic arterial pressure (SAP) and Ppv were determined. 3. In the perfused livers of sedentary rats, antigen administration led to a predominant presinusoidal constriction, as evidenced by 4.6- and 1.7-fold increases in Rpre and Rpost, respectively. The anaphylaxis-induced increase in Rpre was significantly attenuated by 24% by exercise training. Inhibition of NO synthase with NG-nitro-l-arginine methyl ester (100 μmol/L) 10 min prior to the injection of antigen enhanced anaphylactic Venoconstriction, but did not alter the effect of exercise training on the increase in Rpre. In contrast, exercise training did not attenuate either anaphylactic hypotension or portal hypertension in conscious rats. 4. In conclusion, exercise training attenuates the anaphylaxis-induced presinusoidal constriction in rat isolated perfused livers, independent of NO production. However, this action is not evident in conscious rats and exercise training does not affect anaphylactic hypotension in conscious rats.
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leukotrienes and cyclooxygenase products mediate anaphylactic Venoconstriction in ovalbumin sensitized rat livers
European Journal of Pharmacology, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Wei Zhang, Yasutaka KurataAbstract:Hepatic anaphylactic Venoconstriction is partly involved in anaphylactic hypotension. We determined the chemical mediators responsible for anaphylaxis-induced segmental Venoconstriction in perfused livers isolated from ovalbumin-sensitized rats. Livers were perfused portally and recirculatingly at constant flow with diluted blood. The portal venous pressure (Ppv), hepatic venous pressure (Phv), liver weight and hepatic oxygen consumption were continuously measured. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre-sinusoidal (Rpre) and post-sinusoidal (Rpost) resistances. After antigen injection, both Ppv and Pdo increased, resulting in 5.6- and 1.6-fold increases in Rpre and Rpost, respectively. Liver weight showed a biphasic change of an initial decrease followed by an increase. Hepatic oxygen consumption significantly decreased after antigen. Anaphylaxis-induced increase in Rpre was most extensively inhibited by 38.6% by pretreatment with ONO-1078 (100 μM, a cysteinyl leukotriene receptor-1 antagonist), among all antagonists or inhibitors administrated individually including TCV-309 (20 μM), AA-2414 (10 μM), ketanserin (10 μM) and indomethacin (10 μM). Combined pretreatment with indomethacin and ONO-1078 exerted additive inhibitory effects and attenuated Rpre by 65.8%. However, TCV-309, a platelet activating factor (PAF) receptor antagonist, did not affect the anaphylactic response. In contrast, anaphylaxis-induced increase in Rpost was attenuated only by ONO-1078 combined pretreatment. The antigen-induced changes in liver weight and hepatic oxygen consumption were attenuated significantly when hepatic Venoconstriction was attenuated. It is concluded that cysteinyl leukotrienes and cyclooxygenase products, but not PAF, are mainly involved in anaphylaxis-induced pre-sinusoidal constriction in isolated perfused rat livers.
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effects of l name on thromboxane a2 induced Venoconstriction in isolated perfused livers from rat guinea pig and mouse
Vascular Pharmacology, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Zhansheng Zhao, Wei Zhang, Yasutaka KurataAbstract:Abstract Effects of l -NAME on U-46619 (a thromboxane A 2 , analogue) -induced hepatic segmental Venoconstriction were examined in mouse, rat and guinea pig isolated perfused livers. All livers were perfused portally and recirculatingly at a constant flow with diluted blood. U-46619 was administrated into the reservoir in a cumulative manner to gain the concentrations of 0.001–3 μM at 10 min after l -NAME or d -NAME (100 μM). The portal venous pressure, hepatic venous pressure and perfusate flow were monitored. In addition, the sinusoidal pressure was measured by the double occlusion pressure, and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. U-46619 concentration-dependently caused predominant presinusoidal constriction in all three species. The rat livers were the strongest while the mouse livers were the weakest in responsiveness and sensitivity to U-46619. l -NAME mainly augmented the U-46619-induced increases in Rpre, but not in Rpost, in rat and guinea pig. This augmentation was stronger in rat. However, l -NAME did not augment the response to U-46619 in mouse. In conclusion, in rat and guinea pig, NO may be released selectively from the presinusoids in response to U-46619, and then attenuate the U-46619-induced presinusoidal constriction. In mouse, U-46619-induced Venoconstriction is weak and not modulated by NO.
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l name augments paf induced Venoconstriction in isolated perfused livers of rat and guinea pig but not mouse
Prostaglandins Leukotrienes and Essential Fatty Acids, 2007Co-Authors: Toshishige Shibamoto, Hiromichi Takano, Zhansheng Zhao, Yasutaka KurataAbstract:Abstract Platelet-activating factor (PAF), one of vasoconstrictive lipid mediators, is involved in systemic anaphylaxis. On the other hand, nitric oxide (NO) is known to attenuate anaphylactic Venoconstriction of the pre-sinusoids in isolated guinea pig and rat livers. However, it is not known whether NO attenuates PAF-induced hepatic Venoconstriction. We therefore determined the effects of l -NAME, a NO synthase inhibitor, on PAF-induced Venoconstriction in blood- and constant flow-perfused isolated livers of mice, rats and guinea pigs. The sinusoidal pressure was measured by the double occlusion pressure (Pdo), and was used to determine the pre- (Rpre) and post-sinusoidal (Rpost) resistances. PAF (0.01–1 μM) concentration-dependently caused predominant pre-sinusoidal constriction in all livers of three species studied. The guinea pig livers were the most sensitive to PAF, while the mouse livers were the weakest in responsiveness. l -NAME pretreatment selectively increased the basal Rpre in all of three species. l -NAME also significantly augmented the PAF-induced increases in Rpre, but not in Rpost, in rat and guinea pig livers. This augmentation was stronger in rat livers than in guinea pig livers at the high concentration of 0.1 μM PAF. However, l -NAME did not augment PAF-induced Venoconstriction in mouse livers. In conclusion, in rat and guinea pig livers, NO may be released selectively from the pre-sinusoids in response to PAF, and then attenuate the PAF-induced pre-sinusoidal constriction. In mouse liver, PAF-induced Venoconstriction is weak and not modulated by NO.
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ng nitro l arginine methyl ester potentiates anaphylactic Venoconstriction in rat perfused livers
Clinical and Experimental Pharmacology and Physiology, 2006Co-Authors: Toshishige Shibamoto, Takaharu Ishibashi, Tomohiro Shimo, Hiromichi Takano, Hideaki Tsuchida, Matomo Nishio, Yasutaka KurataAbstract:1. The effects of the nitric oxide (NO) synthase inhibitor N G -nitro-L-arginine methyl ester (L-NAME) on anaphylaxisinduced Venoconstriction were examined in rat isolated livers perfused with blood-free solutions in order to clarify the role of NO in anaphylactic Venoconstriction. 2. Rats were sensitized with ovalbumin (1 mg) and, 2 weeks later, livers were excised and perfused portally in a recirculating manner at a constant flow with Krebs'-Henseleit solution. The antigen (ovalbumin; 0.1 mg) was injected into the reservoir 10 min after pretreatment with L-NAME (100 μmol/L) or D-NAME (100 μmol/L) and changes in portal vein pressure (Ppv), hepatic vein pressure (Phv) and perfusate flow were monitored. In addition, concentrations of the stable metabolites of NO (NO - 2 and NO - 3 ) were determined in the perfusate using an HPLC-Griess system. 3. The antigen caused hepatic Venoconstriction, as evidenced by an increase in Ppv from a mean (±SEM) baseline value of 7.7 ± 0.1 cmH 2 O to a peak of 21.4 ± 1.1 cmH 2 O at 3 min in D-NAME-pretreated livers. Pretreatment with L-NAME augmented anaphylactic Venoconstriction, as reflected by a higher Ppv (27.4 ± 0.8 cmH 2 O) after antigen than observed following D-NAME pretreatment. The addition of L-arginine, a precursor for the synthesis of NO, reversed the augmentation of anaphylactic venoconstricion by L-NAME. This suggests that hepatic anaphylaxis increased the production of NO, which consequently attenuated anaphylactic Venoconstriction. However, perfusate NO x levels did not increase significantly after antigen in livers pretreated with either L-NAME or D-NAME. 4. In conclusion, L-NAME potentiates rat anaphylactic hepatic Venoconstriction, suggesting that NO contributes to the attenuation of the Venoconstriction. However, this functional evidence was not accompanied by corresponding changes in perfusate NO x concentrations.
Donal S Oleary - One of the best experts on this subject based on the ideXlab platform.
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active Venoconstriction is is not important in maintaining or raising end diastolic volume and stroke volume during exercise and orthostasis
Journal of Applied Physiology, 2006Co-Authors: Don D Sheriff, Robert A Augustyniak, Donal S OlearyAbstract:The following letter is in response to the Point:Counterpoint “Active Venoconstriction is/is not important in maintaining or raising end-diastolic volume and stroke volume during exercise and orthostasis” that appeared in the October issue. To the Editor : Hainsworth and Drinkhill ([4][1])
David J. Webb - One of the best experts on this subject based on the ideXlab platform.
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endogenous angiotensin ii does not contribute to sympathetic Venoconstriction in dorsal hand veins of healthy humans
Clinical Pharmacology & Therapeutics, 1997Co-Authors: Satoko Masumori, David E Newby, Fiona E Strachan, Nicholas A Boon, David J. WebbAbstract:Background Sympathetically mediated Venoconstriction is augmented by exogenously administered angiotensin II. This study was designed to assess whether endogenous angiotensin II influences sympathetically mediated venous tone. Methods Responses of dorsal hand veins to local intravenous administration of subsystemic doses of losartan, an angiotensin II type-1 receptor antagonist, were assessed with use of a well-validated displacement technique in eight healthy male volunteers. In a four-phase study, responses to local infusions of angiotensin II (4 to 64 ng/min) and norepinephrine (1 to 128 ng/min) or to sympathetic Venoconstriction produced by a single deep breath were compared in the presence of either saline placebo or 30 μg/min losartan. Each phase of the study was conducted on a separate day, in random order, and each phase was separated by at least 1 week. Results Angiotensin II (p = 0.03) and norepinephrine (p < 0.001) caused dose-dependent Venoconstriction. Losartan attenuated the Venoconstriction induced by angiotensin II (p = 0.048) but had no effect on the responses to norepinephrine or the Venoconstriction induced by a single deep breath. Conclusions In contrast to exogenously administered angiotensin II, basal endogenous angiotensin II does not influence sympathetically mediated Venoconstriction in healthy humans. However, endogenous angiotensin II may have a role in circumstances of renin-angiotensin system activation, such as salt depletion. Clinical Pharmacology & Therapeutics (1997) 62, 327–333; doi:
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endothelium dependent modulation of Venoconstriction to sarafotoxin s6c in human veins in vivo
Journal of Cardiovascular Pharmacology, 1995Co-Authors: Fiona E Strachan, William G. Haynes, David J. WebbAbstract:We investigated the vascular effects mediated by ET A and ET B receptors in human dorsal hand veins in vivo, using sarafotoxin S6c (SFTX6c) as a selective agonist of ET B receptors and endothelin-1 (ET-1) as a nonselective agonist of ET A and ET B receptors. The cyclo-oxygenase inhibitor aspirin and the nitric oxide synthase inhibitor L-NMMA were used to examine the modulating role of endothelial vasodilators on the response to SFTX6c. Drugs were all infused into the hand veins, at locally but not systemically active doses, via a 23 SWG butterfly cannula, with the exception of aspirin, which was administered orally. Hand vein size was measured by the Aellig technique. The study was performed in six healthy male subjects. Data (mean ± SEM) were examined by ANOVA. Results are expressed as percent change from baseline at 60 min. ET-1 (5 pmol/min for 60 min) caused Venoconstriction of 68 ± 6% (p = 0.0001). SFTX6c at the same dose caused Venoconstriction of 19 ± 4% (p = 0.003). The response to SFTX6c was significantly less than to ET-1 (p = 0.002). Constriction to SFTX6c tended to increase when this agent was co-administered with aspirin (25 ± 7%) or L-NMMA (24 ± 10%) and was significantly potentiated when these agents were co-administered (45 ± 4% ; p = 0.01 vs. SFTX6c alone). We have demonstrated that the selective ET B agonist SFTX6c produces Venoconstriction in human hand veins in vivo and that this Venoconstriction is modulated by the generation of endothelium-derived vasodilators. In this vascular bed, Venoconstriction rather than venodilatation appears to be the predominant effect of stimulation of ET B receptors with SFTX6c3.
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direct and sympathetically mediated Venoconstriction in essential hypertension enhanced responses to endothelin 1
Journal of Clinical Investigation, 1994Co-Authors: William G. Haynes, Malcolm F Hand, Heather A Johnstone, P L Padfield, David J. WebbAbstract:Endothelin-1 is a potent endothelium-derived vasoconstrictor peptide. Although circulating concentrations are not increased in essential hypertension, enhanced sensitivity to endothelin-1 has been observed in animal models of hypertension. We investigated dorsal hand vein responses to local infusion of endothelin-1 and norepinephrine in 12 patients with essential hypertension who had never received treatment and in 12 age and sex matched normotensive control subjects. The maximal Venoconstriction and the geometric mean of the dose of norepinephrine that caused 50% of maximal Venoconstriction were similar in hypertensive (mean +/- SE; 80 +/- 4%; 31 +/- 8 pmol/min) and normotensive subjects (87 +/- 5%, 22 +/- 9 pmol/min). In contrast, mean Venoconstriction to endothelin-1 was significantly greater in hypertensive (49 +/- 5%) than in normotensive subjects (27 +/- 2%; P = 0.004). Sympathetically mediated Venoconstriction elicited by deep breath was substantially potentiated by endothelin-1 in hypertensive (67 +/- 7% at 90 min) but not normotensive subjects (11 +/- 3% at 90 min; P = 0.001). Venoconstriction to endothelin-1 correlated positively with mean arterial pressure in the hypertensive subjects (r = 0.82; p = 0.001) but negatively in the normotensive subjects (r = -0.58; p = 0.047). Endothelin-1 may contribute to the reduction of venous compliance occurring in the early stages of essential hypertension and to the altered systemic hemodynamics in this condition.
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Venoconstriction to endothelin 1 in humans role of calcium and potassium channels
American Journal of Physiology-heart and Circulatory Physiology, 1993Co-Authors: William G. Haynes, David J. WebbAbstract:: Recent studies in vitro have suggested that there may be an interaction between endothelin-1 and ATP-sensitive K+ channels in vascular smooth muscle. Here we have investigated whether agents acting on membrane Ca2+ and K+ channels modulate endothelin-1-induced Venoconstriction in vivo in human subjects. In a series of studies, six healthy subjects received, on separate occasions, local infusions into dorsal hand veins of endothelin-1 coinfused with 1) the ATP-sensitive K+ channel opener, cromakalim; 2) the dihydropyridine Ca2+ antagonist, nicardipine; 3) a control vasodilator, hydralazine; and 4) saline placebo. Endothelin-1 caused local Venoconstriction with a maximum reduction in vein size of 66 +/- 4% at 60 min (P = 0.0001 vs. basal). Cromakalim prevented endothelin-1-induced Venoconstriction (9 +/- 10% maximum constriction; P = 0.68 vs. basal). By contrast, nicardipine, in a dose sufficient to block depolarization-induced constriction caused by K+ infusion, had only a partial effect on endothelin-1-induced Venoconstriction (35 +/- 8% maximum constriction; P = 0.001 vs. basal; P = 0.02 vs. endothelin-1), whereas a 10-fold higher dose of nicardipine had no additional effect and hydralazine had no effect. In further studies, cromakalim, but not nicardipine, reversed endothelin-1-induced Venoconstriction. Cromakalim did not prevent constriction induced by norepinephrine. Although calcium entry through dihydropyridine-sensitive Ca2+ channels may account in part for the vasoconstrictor action of endothelin-1 in humans, the abolition of endothelin-1 responses by a K+ channel opener suggests additional mechanisms of action for endothelin-1.
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Venoconstriction to endothelin-1 in humans is attenuated by local generation of prostacyclin but not nitric oxide.
Journal of cardiovascular pharmacology, 1993Co-Authors: David J. Webb, William G. HaynesAbstract:Endothelin-1 (ET-1) is known to be a potent and long-lasting constrictor of arteries and veins. We investigated whether local endothelial production of nitric oxide (NO) or prostacyclin modulates Venoconstriction induced by the endothelium-derived peptide ET-1 in vivo in humans. Six healthy volunteers each received local dorsal hand vein infusion of ET-1 (5 pmol/min) for 60 min in five separate studies: once given alone; on three occasions co-infused with either the NO donor glyceryl trinitrate (GTN), the vasodilator prostaglandin, prostacyclin, or the inhibitor of nitric oxide synthase (NOS) NG-monomethyl-arginine (L-NMMA); and once given 30 min after oral administration of the irreversible inhibitor of cyclooxygenase, acetylsalicylic acid (aspirin). ET-1 alone caused slowly developing and long-lasting Venoconstriction (maximal constriction 66 +/- 4%). Although GTN partially prevented ET-1-induced constriction (maximum 33 +/- 5%, p = 0.004 versus ET-1), inhibition of NOS did not affect ET-1-induced Venoconstriction (maximum 55 +/- 4%). Prostacyclin was more effective at blocking the Venoconstriction to ET-1 than GTN (maximum 12 +/- 3%, p = 0.0001) and there was substantial potentiation of ET-1-induced Venoconstriction after pretreatment with aspirin (maximum 90 +/- 3%, p = 0.001). Despite the capacity of NO to attenuate responses to ET-1, L-NMMA did not potentiate ET-1-induced Venoconstriction, suggesting little or no stimulated production of NO by ET-1 in human hand veins. However, substantial potentiation of ET-1-induced Venoconstriction by aspirin indicates that endothelial production of prostacyclin modulates responses to ET-1 in human veins in vivo.
Don D Sheriff - One of the best experts on this subject based on the ideXlab platform.
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active Venoconstriction is is not important in maintaining or raising end diastolic volume and stroke volume during exercise and orthostasis
Journal of Applied Physiology, 2006Co-Authors: Don D Sheriff, Robert A Augustyniak, Donal S OlearyAbstract:The following letter is in response to the Point:Counterpoint “Active Venoconstriction is/is not important in maintaining or raising end-diastolic volume and stroke volume during exercise and orthostasis” that appeared in the October issue. To the Editor : Hainsworth and Drinkhill ([4][1])
