Interaction of nitric oxide and the renin angiotensin system in renal hypertensive rats.
We investigated the interaction between nitric oxide and the renin angiotensin system in regulating isolated aortic tension and mean arterial pressure in renal hypertensive rats (RHR). Acetylcholine (ACh) relaxed aorta precontracted with norepinephrine from RHR significantly less than that from normotensive rats (NR) (Emax: 34.3% and 86.0%, respectively, P < 0.01). The ACh-induced relaxation was significantly enhanced by losartan (P < 0.05) and completely abolished by removal of endothelium or NG-nitro-L-arginine methyl ester (L-NAME). ACh lowered the mean arterial pressure slightly less effectively in RHR than in NR (6.8 and 13.0 mmHg, respectively, at 0.1 microgram/kg), whereas the depressor effect was reduced by L-NAME (-15.5 and 10.3 mmHg, respectively, at 0.1 microgram/kg), but rather enhanced by further treatment with losartan (9.9 (P < 0.05) and 17.3 mmHg, respectively, at 0.1 microgram/kg). Angiotensin II induced similar contractile and pressor responses in both RHR and NR, and these effects were significantly enhanced by L-NAME, except for the pressor effect in RHR. L-NAME induced a similar pressor response in RHR and NR (15.9 and 15.2 mmHg, respectively, at 0.1 mg/kg), the effect being decreased by pretreatment with losartan. Losartan induced a depressor response that was smaller in RHR than in NR (34.0 and 48.8 mmHg, respectively, at 0.3 mg/kg), and the response was significantly reduced by L-NAME. These results suggest that nitric oxide interacts with the renin angiotensin system to control the vascular tension and systemic arterial circulation in RHR.
Lee
B H
BH
Screening and Toxicology Research Center, Korea Research Institute of Chemical Technology, Taejon, Korea.
Shin
H S
HS
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood; D012084:Renin-Angiotensin System / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D012083:Renin; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester