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Richard Laverty - One of the best experts on this subject based on the ideXlab platform.
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effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the Genetically Hypertensive Rat model
Clinical and Experimental Pharmacology and Physiology, 2005Co-Authors: Janet M Ledingham, Richard LavertyAbstract:SUMMARY 1. The aims of the present study were to investigate, in the New Zealand Genetically Hypertensive (GH) Rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance. 2. Genetically Hypertensive Rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly. 3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross-sectional area (CSA), lumen diameter and the Ratio of media width/lumen diameter. 4. Simvastatin monotherapy did not lower BP at either dose. In the high- and low-dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower-dose group. 5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen Ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen Ratio, with the greatest effect observed in the high-dose groups. 6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling. 7. In the basilar artery, high-dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen Ratio independently of any change in BP. 8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and Ratio. In combination with enalapril, there was little consistent additional effect. 9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH Rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.
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endothelial function in mesenteric resistance arteries from the Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2002Co-Authors: Hanzhong Liu, Janet M Ledingham, Ian Mullaney, Richard LavertyAbstract:SUMMARY 1. Endothelial function in mesenteric resistance arteries (MRA) from male 12-week-old New Zealand Genetically Hypertensive (GH) Rats and their normotensive control strain (N) was compared in vessels mounted on a wire myograph and by the production of intracellular cGMP. In parallel experiments, MRA from the spontaneously Hypertensive (SHR) Rat strain, in which there is an endothelial defect, and from GH Rats, in which an endothelial defect was induced by chronic nitric oxide synthase (NOS) inhibition with Nω-nitro-L-arginine methyl ester (L-NAME), were studied. 2. Contractile responses to potassium (124 mmol/L) depolarization and to NA (10–8 to 10–4 mol/L) were similar in GH and N Rats; however, in SHR, enhanced contractile responses were found (P < 0.05). The endothelium-dependent relaxation induced by acetylcholine (ACh; 10–9 to 10–4 mol/L) and endothelium- independent relaxation induced by sodium nitroprusside (SNP; 10–9 to 10–4 mol/L) were identical in prepaRations from GH and N. A significantly attenuated (P < 0.01) vasodilator response to ACh was observed in prepaRations from SHR. 3. Levels of intracellular cGMP were similar in untreated small mesenteric arterial trees from GH, N and SHR Rats. Acetylcholine (10–5 mol/L) significantly (P < 0.001) increased the cGMP content in both GH and N Rats. A non-significant increase occurred in cGMP content in prepaRations from SHR. 4. In GH Rats given L-NAME (10 mg/kg per day for up to 5 weeks), an attenuated (P < 0.01) endothelium-dependent relaxation to ACh and an enhanced (P < 0.01) endothelium- independent relaxation to SNP were observed. Lower basal cGMP levels were found in prepaRations from L-NAME-treated GH Rats and ACh (10–5 mol/L) failed to significantly elevate the cGMP content in these prepaRations. 5. These experiments failed to show evidence of reduced endothelial function in GH Rats, although an endothelial defect in SHR Rats and after NOS inhibition in GH Rats could be demonstRated.
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effects of chronic inhibition of nitric oxide synthase in the Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2000Co-Authors: Elizabeth J Tucker, Janet M Ledingham, Yiwen Zheng, Richard LavertyAbstract:SUMMARY 1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood pressure in the Genetically Hypertensive (GH) Rat strain and NOS activity in regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH and normotensive (N) Rats (n= 7–10 per group) were given NG-nitro- L-arginine methyl ester ( L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7 weeks. Age- and weight-matched controls received water only. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By age 10 weeks, Rats were killed and NOS activity was measured. 3. Some GH Rats that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were killed before the end of the treatment period. 4. No difference in NOS activity was found between untreated N and GH strains but, in those that received treatment, a graded inhibition was observed with increasing L-NAME dose levels. The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS inhibition of 90% where the N strain had 73% inhibition. Similar results were seen in the other areas of the brain. 5. Left ventricular mass, weight related, was significantly greater in the GH compared with N and was further elevated by treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH Rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide synthase inhibition causing increased SBP in GH Rats suggests an abnormality in the nitric oxide–L-arginine pathway in this strain.
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basilar artery remodelling in the Genetically Hypertensive Rat effects of nitric oxide synthase inhibition and treatment with valsartan and enalapril
Clinical and Experimental Pharmacology and Physiology, 2000Co-Authors: Janet M Ledingham, Richard LavertyAbstract:SUMMARY 1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in Genetically Hypertensive (GH) Rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, NG-nitro- L-arginine methyl ester ( L-NAME) and GH given L-NAME and either valsartan or enalapril. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly from age 7–12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined. 3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given L-NAME (P < 0.05). The GH L-NAME + valsartan and GH L-NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH L-NAME group. 4. Basilar arteries in GH (which are frankly Hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen Ratio. 5. In the GH L-NAME group, further inward remodelling occurred and the media to lumen Ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH L-NAME Rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II-stimulated growth was not entirely suppressed with an angiotensin-converting enzyme inhibitor or that there was a bradykinin effect with enalapril. 6. In GH with an endothelial defect induced by treatment with L-NAME, the further remodelling, together with an increased media to lumen Ratio and the development of a stroke-like syndrome, indicates the NOS-inhibited GH Rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.
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nitric oxide synthase inhibition with n omega nitro l arginine methyl ester affects blood pressure and cardiovascular structure in the Genetically Hypertensive Rat strain
Clinical and Experimental Pharmacology and Physiology, 1997Co-Authors: Janet M Ledingham, Richard LavertyAbstract:1. Inhibition of nitric oxide (NO) synthesis with the nitric oxide synthase (NOS) inhibitor N omega-nitro-L-arginine methyl ester (L-NAME) was used as a tool to investigate further a possible endothelial defect in the New Zealand Genetically Hypertensive (GH) Rat strain compared with its normotensive (N) control strain. 2. N omega-nitro-L-arginine methyl ester was given to GH and N groups in their drinking water from age 7-10 weeks (10 mg/kg per day for week 1 and 2 and then 5 mg/kg per day for week 3). Tailcuff blood pressure (BP) was measured weekly and at the end of the experiment the mesentery was fixed by perfusion, second order branches of the mesenteric artery were embedded in Technovit and stained sections were used to quantify the structure of the mesenteric resistance arteries (MRA). The heart was removed and weighed for determination of left ventricular (LV) mass. 3. In GH Rats, BP and LV mass were significantly raised by L-NAME, while in N Rats L-NAME treatment significantly elevated BP, but had no effect on LV mass. 4. In GH Rats, the media width was significantly increased by L-NAME treatment (P < 0.01); lumen diameter remained unchanged. Thus, the Ratio of media width/lumen diameter (M/L) was significantly increased by exacerbation of the hypertrophic outward remodelling characteristic of the GH strain. There were no significant changes in the M/L Ratio in L-NAME-treated N Rats. 5. Thus, in the GH strain, cardiovascular structure is more sensitive to NOS inhibition than either its N control strain or (on evidence from the liteRature) the spontaneously Hypertensive Rat strain.
Janet M Ledingham - One of the best experts on this subject based on the ideXlab platform.
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effect of simvastatin given alone and in combination with valsartan or enalapril on blood pressure and the structure of mesenteric resistance arteries and the basilar artery in the Genetically Hypertensive Rat model
Clinical and Experimental Pharmacology and Physiology, 2005Co-Authors: Janet M Ledingham, Richard LavertyAbstract:SUMMARY 1. The aims of the present study were to investigate, in the New Zealand Genetically Hypertensive (GH) Rat model, the effects of treatment with simvastatin, alone or in combination with valsartan or enalapril, on blood pressure (BP) and structural remodelling of mesenteric resistance arteries (MRA) and of the basilar artery, an artery that plays a major role in the regulation of cerebral resistance. 2. Genetically Hypertensive Rats were treated with simvastatin at two dose levels (5 and 10 mg/kg per day) and simvastatin in combination with valsartan or enalapril (also 5 and 10 mg/kg per day) from the age of 7 to 12 weeks. Systolic BP and bodyweight were measured weekly. 3. At the end of the experiment, following fixation by perfusion, MRA and the basilar artery were excised and embedded in Technovit (a glycol methacrylate medium; Heraeus Kulzer, Werheim, Germany). Serial sections were cut and stereological techniques used to determine tunica media width and cross-sectional area (CSA), lumen diameter and the Ratio of media width/lumen diameter. 4. Simvastatin monotherapy did not lower BP at either dose. In the high- and low-dose groups, the combination of simvastatin + enalapril lowered BP more than with enalapril alone; this was also true for the simvastatin + valsartan combination in the lower-dose group. 5. The MRA were hypotrophically remodelled by the 10 mg/kg per day dose of simvastatin; the 5 mg/kg per day dose caused hypotrophic remodelling with decreased media/lumen Ratio. Valsartan and enalapril caused hypotrophic remodelling together with outward remodelling of the lumen in the 10 mg/kg per day valsartan group and, in all groups, a reduction in the media/lumen Ratio, with the greatest effect observed in the high-dose groups. 6. The combination treatments of simvastatin + valsartan and simvastatin + enalapril did not have any consistent extra effect on MRA remodelling. 7. In the basilar artery, high-dose simvastatin had a hypotrophic effect on the media and both doses reduced the media/lumen Ratio independently of any change in BP. 8. Simvastatin given in combination with valsartan produced a slight further reduction in medial CSA, media width and Ratio. In combination with enalapril, there was little consistent additional effect. 9. Simvastatin monotherapy hypotrophically remodelled the media of the basilar artery in the GH Rat model, even in the absence of changes in BP. A similar structural effect may explain, in part, the reduction in stroke seen in patients treated with statins.
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effect of cross fostering on blood pressure and renal function in the new zealand Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2003Co-Authors: Nick Ashton, Philip A Kelly, Janet M LedinghamAbstract:1. The severity of hypertension displayed by adult spontaneously Hypertensive Rats (SHR) and Dahl (SS/Jr) Rats can be reduced by 20-30 mmHg if the Hypertensive pup is cross-fostered to a normotensive mother within the first 2 weeks of birth. In the SHR, at least, this blood pressure-lowering effect arises through programming of the neonatal kidney to excrete sodium more effectively. Thus, cross-fostering may only be effective in lowering pressure in salt-sensitive Hypertensive strains. Accordingly, the aim of the present study was to determine whether cross-fostering is effective in lowering adult blood pressure in the salt-resistant New Zealand Genetically Hypertensive (GH) Rat. 2. Genetically Hypertensive and control normotensive (N) Rat pups were reared by either their natural mothers or a foster mother of the opposite strain (NX and GHX). Blood pressure was tracked from the age of 6-18 weeks, at which time renal function was assessed using standard clearance techniques in anaesthetized Rats. Renal function was also assessed in a sepaRate group of young Rats at 5-6 weeks of age. 3. Cross-fostered GHX Rats had lower blood pressure than GH Rats, but this difference was only apparent until 9 weeks. The NX Rats had higher blood pressures than N Rats, but again pressure converged at 10 weeks. Basal renal function did not differ between GH and GHX Rats or between N and NX Rats at either age. However, young GH Rats had lower renal blood flow, glomerular filtRation Rate, urine output and sodium excretion than N Rats. 4. These data show that cross-fostering is effective in lowering blood pressure in GH Rats, albeit transiently. The kidneys do not appear to play a role, because renal function did not differ under the current experimental conditions between GH and GHX Rats. However, the kidney may play a greater role in the onset of hypertension in the GH Rat than previously thought.
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endothelial function in mesenteric resistance arteries from the Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2002Co-Authors: Hanzhong Liu, Janet M Ledingham, Ian Mullaney, Richard LavertyAbstract:SUMMARY 1. Endothelial function in mesenteric resistance arteries (MRA) from male 12-week-old New Zealand Genetically Hypertensive (GH) Rats and their normotensive control strain (N) was compared in vessels mounted on a wire myograph and by the production of intracellular cGMP. In parallel experiments, MRA from the spontaneously Hypertensive (SHR) Rat strain, in which there is an endothelial defect, and from GH Rats, in which an endothelial defect was induced by chronic nitric oxide synthase (NOS) inhibition with Nω-nitro-L-arginine methyl ester (L-NAME), were studied. 2. Contractile responses to potassium (124 mmol/L) depolarization and to NA (10–8 to 10–4 mol/L) were similar in GH and N Rats; however, in SHR, enhanced contractile responses were found (P < 0.05). The endothelium-dependent relaxation induced by acetylcholine (ACh; 10–9 to 10–4 mol/L) and endothelium- independent relaxation induced by sodium nitroprusside (SNP; 10–9 to 10–4 mol/L) were identical in prepaRations from GH and N. A significantly attenuated (P < 0.01) vasodilator response to ACh was observed in prepaRations from SHR. 3. Levels of intracellular cGMP were similar in untreated small mesenteric arterial trees from GH, N and SHR Rats. Acetylcholine (10–5 mol/L) significantly (P < 0.001) increased the cGMP content in both GH and N Rats. A non-significant increase occurred in cGMP content in prepaRations from SHR. 4. In GH Rats given L-NAME (10 mg/kg per day for up to 5 weeks), an attenuated (P < 0.01) endothelium-dependent relaxation to ACh and an enhanced (P < 0.01) endothelium- independent relaxation to SNP were observed. Lower basal cGMP levels were found in prepaRations from L-NAME-treated GH Rats and ACh (10–5 mol/L) failed to significantly elevate the cGMP content in these prepaRations. 5. These experiments failed to show evidence of reduced endothelial function in GH Rats, although an endothelial defect in SHR Rats and after NOS inhibition in GH Rats could be demonstRated.
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effects of chronic inhibition of nitric oxide synthase in the Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2000Co-Authors: Elizabeth J Tucker, Janet M Ledingham, Yiwen Zheng, Richard LavertyAbstract:SUMMARY 1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood pressure in the Genetically Hypertensive (GH) Rat strain and NOS activity in regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH and normotensive (N) Rats (n= 7–10 per group) were given NG-nitro- L-arginine methyl ester ( L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7 weeks. Age- and weight-matched controls received water only. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By age 10 weeks, Rats were killed and NOS activity was measured. 3. Some GH Rats that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were killed before the end of the treatment period. 4. No difference in NOS activity was found between untreated N and GH strains but, in those that received treatment, a graded inhibition was observed with increasing L-NAME dose levels. The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS inhibition of 90% where the N strain had 73% inhibition. Similar results were seen in the other areas of the brain. 5. Left ventricular mass, weight related, was significantly greater in the GH compared with N and was further elevated by treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH Rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide synthase inhibition causing increased SBP in GH Rats suggests an abnormality in the nitric oxide–L-arginine pathway in this strain.
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basilar artery remodelling in the Genetically Hypertensive Rat effects of nitric oxide synthase inhibition and treatment with valsartan and enalapril
Clinical and Experimental Pharmacology and Physiology, 2000Co-Authors: Janet M Ledingham, Richard LavertyAbstract:SUMMARY 1. The structure of the basilar artery and the relationship of structure to blood pressure and ventricular hypertrophy was examined in Genetically Hypertensive (GH) Rats, their control normotensive (N) Wistar strain, GH given the nitric oxide synthase (NOS) inhibitor, NG-nitro- L-arginine methyl ester ( L-NAME) and GH given L-NAME and either valsartan or enalapril. 2. Systolic blood pressure (SBP; tail-cuff) was measured weekly from age 7–12 weeks. At the end of the experiment at 12 weeks, the basilar artery was fixed by perfusion and embedded in Technovit (Heraeus Kulzer GmbH, Werheim, Germany). Serial sections were cut and stained and stereological analysis applied to quantify the morphology of the vessels. Left ventricular (LV) mass was determined. 3. Both SBP and LV mass were significantly increased in GH compared with N (P < 0.001) and increased further in GH given L-NAME (P < 0.05). The GH L-NAME + valsartan and GH L-NAME + enalapril groups had significantly lower (P < 0.001) SBP and LV mass than the GH L-NAME group. 4. Basilar arteries in GH (which are frankly Hypertensive, but have no apparent endothelial defect) showed hypotrophic inward remodelling compared with the N control group with no change in media to lumen Ratio. 5. In the GH L-NAME group, further inward remodelling occurred and the media to lumen Ratio was increased compared with N (P < 0.01) and GH (P < 0.05). Valsartan treatment in GH L-NAME Rats caused eutrophic outward remodelling. Enalapril caused hypertrophic outward remodelling, suggesting that the angiotensin II-stimulated growth was not entirely suppressed with an angiotensin-converting enzyme inhibitor or that there was a bradykinin effect with enalapril. 6. In GH with an endothelial defect induced by treatment with L-NAME, the further remodelling, together with an increased media to lumen Ratio and the development of a stroke-like syndrome, indicates the NOS-inhibited GH Rat may be a useful model for essential hypertension (where it is known that endothelial abnormalities exist) and where stroke can develop as a consequence of the hypertension.
J A Millar - One of the best experts on this subject based on the ideXlab platform.
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remodelling of resistance arteries by treatment with enalapril in the new zealand Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 1994Co-Authors: Janet M Ledingham, E L Phelan, Richard Laverty, M Cross, J A MillarAbstract:SUMMARY 1. New Zealand Genetically Hypertensive (GH) Rats were treated with enalapril from the age of 4 to 10 weeks and the effects of treatment on the structure of mesenteric resistance arteries (MR A) was measured by use of stereological analysis of stained sections and by myograph techniques. 2. Tail-cuff blood pressure (BP) was measured weekly and intra-arterial BP recorded just before MRA were either fixed by perfusion or mounted on a myograph. 3. Stereological techniques (Cavalieri and optical dissector) were used to determine media and lumen volume, fraction of smooth muscle (SM) within the media and SM cell density. For MRA mounted on the myograph, lumen diameter, media thickness, active tension and active pressure were recorded. 4. BP was significantly (P<0.0001) lowered by enalapril throughout the experiment. Intra-arterial BP and left ventricular (LV) mass were also significantly lower in the enalapril treated GH Rats (P<0.0001). 5. Stereological measurements showed that enalapril treatment significantly (P<0.0001 reduced media volume by 50%, doubled lumen volume (P<0.0001)), reduced the fraction of SM in the media (P<0.04), and had no effect on the number of SM cell layers or on SM cell density. 6. Myograph measurements showed a decrease in the Ratio media thickness/lumen diameter which was accompanied by a decrease in maximum active tension and pressure development. 7. In the GH Rat early treatment with enalapril causes a true loss of medial tissue that is not simply due to rearrangement of existing media around an enlarged lumen. 8. The reduction in media without changes in SM cell density or in the number of layers of SM cells supports the suggestion that angiotensin-converting enzyme (ACEI) have an effect on cell matrix.
Elizabeth J Tucker - One of the best experts on this subject based on the ideXlab platform.
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effects of chronic inhibition of nitric oxide synthase in the Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2000Co-Authors: Elizabeth J Tucker, Janet M Ledingham, Yiwen Zheng, Richard LavertyAbstract:SUMMARY 1. The effects of graded inhibition of nitric oxide synthase (NOS) on blood pressure in the Genetically Hypertensive (GH) Rat strain and NOS activity in regions of the brain (cerebellum, striatum, hippocampus, frontal cortex and medulla oblongata) as a measure of body NOS inhibition were studied. 2. Male GH and normotensive (N) Rats (n= 7–10 per group) were given NG-nitro- L-arginine methyl ester ( L-NAME; 2, 5, 10 or 20 mg/kg per day in drinking water) from age 7 weeks. Age- and weight-matched controls received water only. Systolic blood pressure (SBP) was measured weekly by the tail-cuff method from age 6 weeks. By age 10 weeks, Rats were killed and NOS activity was measured. 3. Some GH Rats that received over 5 mg/kg per day L-NAME developed stroke-like symptoms and were killed before the end of the treatment period. 4. No difference in NOS activity was found between untreated N and GH strains but, in those that received treatment, a graded inhibition was observed with increasing L-NAME dose levels. The frontal cortex in the GH strain given 20 mg/kg per day L-NAME had NOS inhibition of 90% where the N strain had 73% inhibition. Similar results were seen in the other areas of the brain. 5. Left ventricular mass, weight related, was significantly greater in the GH compared with N and was further elevated by treatment with L-NAME. 6. The SBP at 10 weeks was significantly elevated in GH Rats by NOS inhibition with L-NAME in a dose-dependent manner; 25% for 2 mg/kg per day, 31% for 20 mg/kg per day (P < 0.001). There was a non-significant increase in BP in the N-treated groups (average change of 7.5%). 7. Nitric oxide synthase inhibition causing increased SBP in GH Rats suggests an abnormality in the nitric oxide–L-arginine pathway in this strain.
Nick Ashton - One of the best experts on this subject based on the ideXlab platform.
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effect of cross fostering on blood pressure and renal function in the new zealand Genetically Hypertensive Rat
Clinical and Experimental Pharmacology and Physiology, 2003Co-Authors: Nick Ashton, Philip A Kelly, Janet M LedinghamAbstract:1. The severity of hypertension displayed by adult spontaneously Hypertensive Rats (SHR) and Dahl (SS/Jr) Rats can be reduced by 20-30 mmHg if the Hypertensive pup is cross-fostered to a normotensive mother within the first 2 weeks of birth. In the SHR, at least, this blood pressure-lowering effect arises through programming of the neonatal kidney to excrete sodium more effectively. Thus, cross-fostering may only be effective in lowering pressure in salt-sensitive Hypertensive strains. Accordingly, the aim of the present study was to determine whether cross-fostering is effective in lowering adult blood pressure in the salt-resistant New Zealand Genetically Hypertensive (GH) Rat. 2. Genetically Hypertensive and control normotensive (N) Rat pups were reared by either their natural mothers or a foster mother of the opposite strain (NX and GHX). Blood pressure was tracked from the age of 6-18 weeks, at which time renal function was assessed using standard clearance techniques in anaesthetized Rats. Renal function was also assessed in a sepaRate group of young Rats at 5-6 weeks of age. 3. Cross-fostered GHX Rats had lower blood pressure than GH Rats, but this difference was only apparent until 9 weeks. The NX Rats had higher blood pressures than N Rats, but again pressure converged at 10 weeks. Basal renal function did not differ between GH and GHX Rats or between N and NX Rats at either age. However, young GH Rats had lower renal blood flow, glomerular filtRation Rate, urine output and sodium excretion than N Rats. 4. These data show that cross-fostering is effective in lowering blood pressure in GH Rats, albeit transiently. The kidneys do not appear to play a role, because renal function did not differ under the current experimental conditions between GH and GHX Rats. However, the kidney may play a greater role in the onset of hypertension in the GH Rat than previously thought.