Studies on the glomerular microcirculatory actions of manidipine and its modulation of the systemic and renal effects of endothelin

Kihito Takahashi, Tetsuo Katoh, Megumu Fukunaga, Kamal F. Badr

Research output: Contribution to journalArticle

Abstract

We examined the actions of intravenously administered manidipine on systemic and renal microcirculatory hemodynamics and its efficacy in antagonizing endothelin-1 (ET-1)-evoked responses. Manidipine was a potent vasodilator with preferential activity in the renal vasculature. Its administration in optimal doses resulted in decreases in systemic arterial pressures accompanied by increases in renal perfusion and filtration rates. Its primary sites of action in the kidney were at both pre- and postglomerular arteriolar sites. Manidipine was capable of near-total reversal of the sustained elevations in arterial pressure and the progressive reductions in renal blood flow and glomerular filtration rates induced by intravenously administered ET-1. In the presence of prolonged calcium channel blockade, subsequent administration of ET-1 led to paradoxic hypotensive responses, which could be profound and blocked by an inhibitor of nitric oxide synthesis. These unexpected vasorelaxant actions of ET-1 in the presence of manidipine were likely caused by the dual effects of antagonism of its own intrinsic vasoconstrictor action (through calcium channel blockade), as well as ET-1-evoked release of the endothelium-derived relaxing factor, nitric oxide.

Original languageEnglish (US)
Pages (from-to)609-619
Number of pages11
JournalAmerican Heart Journal
Volume125
Issue number2 PART 2
DOIs
StatePublished - 1993
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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