Cardiovascular responses to angiotensins I and II in normotensive and hypertensive rats; effects of NO synthase inhibition or ET receptor antagonism.
1. We compared the cardiovascular responses to angiotensins (I and II), and any possible modulatory influences thereupon of nitric oxide (NO) or endothelin (ET) in conscious male, normotensive, Hannover Sprague-Dawley (SD) rats, and hypertensive, heterozygous ((mRen-2)27), transgenic (TG) rats. 2. The pressor effects of angiotensin I or of angiotensin II were not consistently different in SD and TG rats. The accompanying absolute reductions in renal and mesenteric vascular conductances were smaller in TG rats, but probably due to the baseline vasoconstriction in those animals. 3. Inhibition of NO synthase with L-NAME had no significant effects on the pressor responses to angiotensin I or angiotensin II in either SD or TG rats. L-NAME reduced the absolute, but not percentage, reductions in renal and mesenteric vascular conductances in response to angiotensin I and angiotensin II. L-NAME abolished the hindquarters vasodilator effects of angiotensin I and angiotensin II in both strains of rat. 4. ET receptor antagonism (with SB209670) had no significant influence on the pressor or renal or mesenteric vasoconstrictor effects of angiotensin II in SD rats. In TG rats, the pressor responses to angiotensin II were unaffected by SB209670; the accompanying falls in renal and mesenteric vascular conductances were enhanced in absolute, but not in percentage terms. 5. These results provide no evidence for a buffering action of NO, or a modulatory influence of ET, on the pressor or vasoconstrictor effects of angiotensin I and/or angiotensin II in SD rats. Furthermore, there is no evidence for an altered sensitivity to angiotensin I or angiotensin II, and no evidence for a differential modulatory influence of either NO or ET in TG, compared to SD, rats.
Gardiner
S M
SM
School of Biomedical Sciences, University of Nottingham Medical School, Queen's Medical Centre, Nottingham NG7 2UH, UK.
March
J E
JE
Kemp
P A
PA
Bennett
T
T
D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects* / Q000235:genetics; D006973:Hypertension / Q000235:genetics*; D007189:Indans / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D065128:Endothelin Receptor Antagonists; D004791:Enzyme Inhibitors; D007189:Indans; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; C087551:1H-Indene-2-carboxylic acid, 1-(1,3-benzodioxol-5-yl)-3-(2- (carboxymethoxy)-4-methoxyphenyl)-2,3-dihydro-5-propoxy-, (1S,2R,3S)-; D000804:Angiotensin II; D000803:Angiotensin I; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester