Acidosis-induced coronary constriction in the rat heart: Evidence for the activation of L-type calcium channels

Abstract

Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

Changes in pH Increase Perfusion Pressure of Coronary Arteries in the Rat

“…Changing the pH of the perfusate from 7.4 to alkaline pH resulted in an increase of coronary perfusion pressure in both WKY and SHR, confirming previous reports (5,19). However, effects of acidic pH on coronary arteries in normotensive rats have been controversial (8,18). Moreover, previous reports paid no attention to the blood pressure in rats.…”

“…However, previous reports were controversial. While, it was reported that acidosis caused vasodilation in coronary arteries of the Sprague-Dawley rat (8), pig (15,16), and dog (17), Wilson and Woodward (18) reported that acidosis induced coronary constriction in the rat heart. The animals used in these reports were all normotensive, and the effect of acidosis on coronary arteries in hypertensive animals was not investigated.…”

Regulation of Human Coronary Vascular Tone: Further Evidence Must Be Sought Before Ruling Out the Direct Role of ATP-Sensitive Potassium Channels in Regulation of Coronary Vasculature

“…2 What makes the disparity in the 2 models more substantial is the evidence in literature that acidosis had induced contraction of VSM in other rodent models as well. 6 A direct implication of VSM K ϩ ATP channels has been elucidated in control of vasculature tone in an isolated study by Wang et al on rodent vasculature as well. Therefore, we cannot disregard the fact that the study was on mesenteric vasculature and the results cannot be generalized to coronary vasculature.…”

Extracellular acidosis contracts coronary but neither renal nor mesenteric artery via modulation of H+,K+‐ATPase, voltage‐gated K+ channels and L‐type Ca2+ channels

“…On the contrary, it was also reported that acidosis decreased coronary blood flow in anaesthetized dogs (Goodyer et al . ), increased coronary perfusion pressure (vasoconstriction) in rat isolated heart (Wilson & Woodward, ) and contracted RCA in both wire‐mounted rings and cannulated isolated RCA segments (Baxter et al . ).…”

“…; Lindauer et al . ), L‐type voltage‐gated Ca 2+ channels (LVGCs; Wilson & Woodward, ), ATP‐sensitive K + (K ATP ) channels (Ishizaka & Kuo, ), nitric oxide (Celotto et al . ) and prostanoids (Celotto et al .…”