T-type and L-type calcium channel blockers exert opposite effects on renin secretion and renin gene expression in conscious rats

British Journal of Pharmacology
C WagnerA Kurtz

Abstract

1. This study aimed to investigate and to compare the effects of pharmacological T-type calcium channel and of L-type calcium channel blockade on the renin system. To this end, male healthy Sprague-Dawley rats were treated with the T-channel blocker mibefradil or with the L-channel blocker amlodipine at doses of 5 mg kg(-1), 15 mg kg(-1) and 45 mg kg(-1) per day for four days and their effects on plasma renin activity (PRA) and kidney renin mRNA levels were determined. 2. Whilst amlodipine lowered basal systolic blood pressure at 5 mg kg(-1), mibefradil had no effect on basal blood pressure in the whole dose range examined. Amlodipine dose-dependently induced up to 7 fold elevation of PRA and renin mRNA levels. Mibefradil significantly lowered PRA and renin mRNA levels at 5 mg kg(-1) and moderately increased both parameters at a dose of 45 mg kg(-1), when PRA and renin mRNA levels were increased by 100% and 30%, respectively. In primary cultures of renal juxtaglomerular cells neither amlodipine nor mibefradil (0.1-10 microM) changed renin secretion. 3. In rats unilateral renal artery clips (2K-1C) mibefradil and amlodipine at doses of 15 mg kg(-1) day(-1) were equally effective in lowering blood pressure. In contrast mibefradil...Continue Reading

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Citations

Dec 3, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Masanori AbeMasayoshi Soma
Jun 4, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shinji TakaiMizuo Miyazaki
Oct 6, 2007·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Toshinari TanakaMinoru Horie
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Oct 5, 2016·Expert Opinion on Investigational Drugs·J Tamargo, Luis Miguel Ruilope
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Jul 16, 2008·Bioorganic & Medicinal Chemistry Letters·Hyung Kook LeeKye Jung Shin
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Feb 20, 2007·Circulation Research·Koichi HayashiTakao Saruta
Nov 19, 2005·Journal of Pharmacological Sciences·Hikaru Tanaka, Koki Shigenobu
Nov 19, 2005·Journal of Pharmacological Sciences·Koichi HayashiTakao Saruta
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Jul 2, 2020·International Journal of Nephrology and Renovascular Disease·Zsolt Razga
Dec 19, 2014·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Pernille B L Hansen

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