L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil.
Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Küng
C F
CF
Division of Cardiology, University Hospital, Bern, Switzerland.
Moreau
P
P
Takase
H
H
Lüscher
T F
TF
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology*; D001120:Arginine / Q000031:analogs & derivatives; D001794:Blood Pressure / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D007211:Indoles / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000378:metabolism / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use; D014700:Verapamil / Q000627:therapeutic use
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D014665:Vasodilator Agents; C052035:trandolapril; D001120:Arginine; D014700:Verapamil; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester