Differential effects of the calcium antagonist, nisoldipine, versus the arterial vasodilator, minoxidil, on ventricular anatomy, intravascular volume, and sympathetic activity in rats.
Opposite effects on cardiac volume load or sympathetic activity by calcium-antagonists versus classical arterial vasodilators may be responsible for their different effects on ventricular anatomy, [i.e., left ventricular (LV) and right ventricular (RV) weights and LV internal diameter and wall thickness.] Therefore, we evaluated the time course of changes in intravascular volume and ventricular anatomy in unanesthetized normotensive rats, following treatment for 1, 2, 14, 35, or 70 days with minoxidil (120 mg/L drinking water) or nisoldipine (0.3 and 1.0 mg/g food). Tissue-specific sympathetic activity was assessed by the norepinephrine turnover rate (NE TR) after 14 and 35 days of treatment. Minoxidil produced RV hypertrophy and eccentric LV hypertrophy (i.e., increased LV diameter with unchanged wall thickness) and increased intravascular volume. Nisoldipine did not alter LV anatomy, but the high dose produced a small, significant increase in RV weight, associated with a tendency (p less than 0.1) to increase blood volume. Minoxidil increased NE TR in the LV (after 14 and 35 days), in the RV (after 14 days), as well as in the superior mesenteric artery (after 14 and 35 days), but not in the kidney. Nisoldipine decreased cardiac NE TR, but did not affect NE TR in the other tissues, suggesting a central effect of nisoldipine. We conclude that an increase in blood volume caused by arterial vasodilators may contribute to cardiac volume overload resulting in cardiac hypertrophy. These volume and cardiac changes are largely absent during treatment with calcium-antagonists. Changes in cardiac sympathetic activity possibly modulate (i.e., potentiate or blunt) the extent of cardiac hypertrophy induced by cardiac overload.
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Division of Clinical Pharmacology, Toronto Western Hospital, Ontario, Canada.
Tsoporis
J
J
Leenen
F H
FH
D000818:Animals; D001810:Blood Volume / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D004326:Drinking / Q000187:drug effects; D004435:Eating / Q000187:drug effects; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D015737:Nisoldipine / Q000097:blood / Q000494:pharmacology*; D009638:Norepinephrine / Q000097:blood; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D013564:Sympathetic Nervous System / Q000187:drug effects*
D002395:Catecholamines; D015737:Nisoldipine; D008914:Minoxidil; D009638:Norepinephrine