Effect of calcium antagonists and other drugs on the hypoxia-induced increase in rat right ventricular pressure.
The effect of four calcium antagonists (nifedipine, nitrendipine, nisoldipine, and verapamil) on hypoxia-induced changes in right ventricular parameters were examined in anesthetized closed-chest rats using an ultraminiature catheterization technique. The effect of the calcium antagonists was compared to the alpha-adrenoceptor blocker prazosin, the beta-adrenoceptor blocker propranolol, the angiotensin-converting enzyme (ACE) inhibitor captopril, and the vasodilator nitroglycerin. The animals were exposed to two successive 5-min hypoxic periods separated by a normoxic interval of 60 min, during which the animals received an intravenous (i.v.) infusion of the substances tested. Hypoxia caused a marked rise in right ventricular systolic pressure (RVSP) and a moderate increase in RVdP/dtmax. Heart rate (HR) was only slightly enhanced. The functional response to the second hypoxic period did not differ from the first one in NaCl-infused animals. All calcium antagonists reduced the hypoxic pressure increase in a dose-dependent manner and ultimately abolished it. Nisoldipine was the most effective substance, followed by nifedipine, nitrendipine, and verapamil. In contrast, prazosin and propranolol did not influence the hypoxic pressure response. Administration of captopril and nitroglycerin attenuated the increase in RVSP. Thus, as compared with the other substances tested, calcium antagonists were the most effective drugs that antagonized the hypoxia-induced increase in RVSP.
Zierhut
W
W
Department of Physiology, University of Munich, F.R.G.
Zimmer
H G
HG
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002216:Captopril / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D005996:Nitroglycerin / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D002121:Calcium Channel Blockers; D002216:Captopril; D011433:Propranolol; D005996:Nitroglycerin; D011224:Prazosin