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, IC) 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). We conclude that effective blood pressure (BP) reduction results in regression of the morphologic changes of resistance arteries of 2-K, 1 C hypertensive rats and normalizes blunted responses to endothelin-1 and other agents in these blood vessels. Whether these effects are only a result of BP reduction or of other phenomena remains to be established.