Vascular responsiveness to nitric oxide synthesis inhibition in hypertensive rats.
We contrasted in normotensive and hypertensive rats the effect of inhibition of nitric oxide synthesis on isometric tension development by aortic rings bathed in Krebs' bicarbonate buffer. NG-Nitro-L-arginine methyl ester (L-NAME) (3 x 10(-4) mol/L) increased tension (82 +/- 11% of the response to 120 mmol/L potassium chloride) in rings of thoracic aorta taken from hypertensive rats 7 to 14 days after aortic coarctation, whereas rings of abdominal aorta from below the coarctation were unresponsive, as were rings of thoracic aorta from rats with deoxycorticosterone-salt-induced hypertension and from the corresponding normotensive controls of either model of hypertension. The contractile response to L-NAME in aortic rings of rats with aortic coarctation was reversed by L-arginine (1 mmol/L), attenuated by removal of the endothelium, and blunted by the protein kinase C inhibitor staurosporine but was unaffected by inhibition of cyclooxygenase, scavengers of superoxide anion, or blockade of receptors for angiotensin, norepinephrine, serotonin, or endothelin. In additional experiments we contrasted the effect of L-NAME (10 mg/kg IV) on the blood pressure of sham-operated rats and rats with aortic coarctation after pretreatment of animals in both groups with DuP 753 (30 mg/kg IV) to achieve blood pressure equalization. The pressor response to L-NAME was twofold greater in rats with aortic coarctation than in sham-operated controls. That pressor and aortic constrictor responsiveness to L-NAME are increased after aortic coarctation suggests that a mechanism of vasodilation, mediated by nitric oxide, is preferentially manifested in rats with aortic coarctation-induced hypertension.
Pucci
M L
ML
Department of Pharmacology, New York Medical College, Valhalla 10595.
Miller
K B
KB
Dick
L B
LB
Guan
H
H
Lin
L
L
Nasjletti
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology*; D001017:Aortic Coarctation / Q000150:complications; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D006973:Hypertension / Q000209:etiology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D010656:Phenylephrine; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D008751:Methylene Blue; D019331:NG-Nitroarginine Methyl Ester