Effect of antihypertensive treatment on response to endothelin of resistance arteries of hypertensive rats.
In other studies, we noted decreased reactivity of resistance arteries to endothelin-1 (ET-1) in hypertensive rats and humans. To determine whether these changes are reversible with antihypertensive treatment, we examined a hypertensive model exquisitely sensitive to angiotensin I-converting enzyme (ACE) inhibition, the two-kidney, one-clip (2K, 1C) Goldblatt hypertensive rat. Rats were allowed to become hypertensive for 6 weeks. At this point, either the clip was removed, or rats were treated with 5-10 mg/kg/day cilazapril, 100-150 mg/kg/day metoprolol, or 25 mg/kg/day hydralazine, or were left untreated. After 8 weeks more, mesenteric resistance arteries were examined after mounting on a wire-myograph. Blood pressure (BP) and heart/body weight ratio were normalized in unclipped and cilazapril-treated rats. Plasma renin activity (PRA) was normalized only in the unclipped group. Media width, media/lumen ratio, and media cross-sectional area were similar in control normotensive, unclipped, and cilazapril-treated rats and increased in untreated hypertensive, metoprolol, and hydralazine groups. Dose-response curves of resistance arteries to ET-1 were significantly blunted in untreated hypertensive rats (maximum active tension = 2.3 +/- 0.3 vs 3.4 +/- 0.1 N/m in control, p < 0.01), metoprolol-treated (2.2 +/- 0.4 N/m), and hydralazine-treated rats (2.1 +/- 0.5 N/m), and were normalized in cilazapril (3.3 +/- 0.1 N/m) and unclipped rats (3.2 +/- 0.1 N/m). Similar effects were noted in response to norepinephrine (NE) and arginine vasopressin (AVP).(ABSTRACT TRUNCATED AT 250 WORDS)
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Experimental Hypertension Laboratory, Clinical Research Institute of Montreal, Quebec, Canada.
Schiffrin
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D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001127:Arginine Vasopressin / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D017315:Cilazapril / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000627:therapeutic use; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D066298:In Vitro Techniques; D017537:Mesenteric Artery, Inferior / Q000187:drug effects; D008790:Metoprolol / Q000627:therapeutic use; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009638:Norepinephrine / Q000097:blood; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000097:blood
D000959:Antihypertensive Agents; D016232:Endothelins; D001127:Arginine Vasopressin; D017315:Cilazapril; D006830:Hydralazine; D012083:Renin; D008790:Metoprolol; D009638:Norepinephrine