Calcium antagonists and hypertension.
1. Calcium antagonists, including verapamil, are now used widely in the management of patients with hypertension. 2. Six weeks of chronic therapy with verapamil (50 mg/kg per day, orally) to produce a plasma level of 80-100 ng/ml in Sprague-Dawley rats depletes cardiac noradrenaline (NA) without apparently causing beta 1 adrenoceptor 'up' regulation. 3. The effect of verapamil on cardiac NA is rapidly reversed upon verapamil withdrawal. 4. Chronic therapy with nisoldipine (100 mg/kg per day, orally) had no effect on cardiac NA. 5. Verapamil (50 mg/kg per day, orally) and nisoldipine (100 mg/kg per day, orally) therapy for 6 weeks prevented the time-dependent increase in systolic blood pressure in SHR rats. 6. Binding studies with (-)[3H]-D888 (desmethoxyverapamil) indicated that the affinity of the phenylalkylamine binding sites is higher in hearts of SHR relative to hearts from age-matched (25 weeks) WKY and SD, without any change in density.
Nayler
W G
WG
Department of Medicine, University of Melbourne, Austin Hospital, Heidelberg, Victoria, Australia.
Dillon
J S
JS
Sturrock
W J
WJ
D000375:Aging / Q000378:metabolism; D000814:Aniline Compounds / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002395:Catecholamines / Q000378:metabolism; D004082:Dihydroalprenolol; D006321:Heart / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D015737:Nisoldipine / Q000097:blood / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000378:metabolism; D014700:Verapamil / Q000097:blood / Q000494:pharmacology
D000814:Aniline Compounds; D002121:Calcium Channel Blockers; D002395:Catecholamines; D011943:Receptors, Adrenergic, beta; D015737:Nisoldipine; D004082:Dihydroalprenolol; D014700:Verapamil; D009638:Norepinephrine