Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K(+ATP) channels

R. K. Minkes, Peter Kvamme, T. R. Higuera, B. D. Nossaman, P. J. Kadowitz

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Abstract

Cardiovascular and pulmonary responses to cromakalim, a member of a novel class of antihypertensive agents that open ATP-sensitive K+ (K(+ATP)) channels, were investigated in the anesthetized cat. Intravenous injections of cromakalim in doses of 30-300 μg/kg decreased arterial pressure (AP), pulmonary arterial pressure (PAP), and increased cardiac output (CO), while producing small changes in right and left atrial pressures. Pulmonary and systemic vascular resistances were decreased and vasodilator responses to cromakalim were blocked by glybenclamide, a K(+ATP) channel-blocking agent. The low dose of cromakalim caused a reflex increase in heart rate (HR) and right ventricular contractile force (RVCF), whereas the high dose decreased HR and RVCF. Under constant-flow conditions the K(+ATP) channel opener caused dose-dependent decreases in hindquarters perfusion pressure, and when tone was elevated in the pulmonary vascular bed, dose-dependent decreases in pulmonary lobar arterial perfusion pressure. Hindquarters and pulmonary lobar vasodilator responses to cromakalim were inhibited in a specific manner by glybenclamide. The present data show that cromakalim has significant vasodilator activity in both the systemic and pulmonary vascular beds and suggest that responses to this agent result from activation of glybenclamide-sensitive K(+ATP) channels. These data show that cromakalim can cause substantial decreases in systemic and pulmonary vascular resistance in a dose that has little effect on RVCF.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume260
Issue number3 29-3
StatePublished - Apr 29 1991
Externally publishedYes

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Cromakalim
Blood Vessels
Adenosine Triphosphate
Lung
Vascular Resistance
Glyburide
Vasodilator Agents
Arterial Pressure
Perfusion
Heart Rate
Atrial Pressure
Intravenous Injections
Cardiac Output
Antihypertensive Agents
Reflex
Cats
Pressure

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Analysis of pulmonary and systemic vascular responses to cromakalim, an activator of K(+ATP) channels. / Minkes, R. K.; Kvamme, Peter; Higuera, T. R.; Nossaman, B. D.; Kadowitz, P. J.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 260, No. 3 29-3, 29.04.1991.

Research output: Contribution to journalArticle

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