Contribution of nitric oxide to coronary vasodilation during hypercapnic acidosis

Abstract

The present study was performed to evaluate the role of nitric oxide (NO) in coronary vasodilation during hypercapnic acidosis (HC). The left anterior descending coronary arteries of 17 anesthetized, open-chest dogs were perfused with normal arterial blood or with arterial blood equilibrated in an extracorporeal circuit with 90% O2-10% CO2 [arterial carbon dioxide tension (PaCO2) 72 +/- 3 mmHg, arterial pH 7.16 +/- 0.02]. Coronary perfusion pressure (CPP) was initially set at 100 mmHg. Coronary blood flow (CBF) was measured with a Doppler transducer. Studies were conducted under constant-pressure (variable CBF; n = 13) and constant-flow (variable CPP) conditions (n = 4). Steady-state changes in CBF (or CPP) during HC and during intracoronary infusions of acetylcholine (ACh, 20 micrograms/min), an endothelium-dependent vasodilator, and sodium nitroprusside (SNP, 80 micrograms/min), an endothelium-independent vasodilator, were compared before and after intracoronary infusion of a NO synthase inhibitor, either NG-nitro-L-arginine methyl ester (L-NAME, 4.5 mg) or NG-monomethyl-L-arginine (L-NMMA, 30 mg). Under constant pressure, L-NAME blunted increases in CBF by HC (274 +/- 32 vs. 113 +/- 24%) and ACh (400 +/- 43 vs. 68 +/- 17%), whereas increases in CBF by SNP were not significantly affected (207 +/- 34 vs. 186 +/- 18%). Results with L-NMMA were similar. Under constant flow, L-NAME attenuated decreases in CPP by HC and ACh, whereas it had no significant effect on decreases in CPP by SNP. In conclusion, HC elicits release of NO from coronary vascular endothelium via a direct effect rather than secondary to an increased flow rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Involvement of barium‐sensitive K+ channels in endothelium‐dependent vasodilation produced by hypercapnia in rat mesenteric vascular beds

“…The importance of the endothelium for the vasodilatory e ect of CO 2 has been demonstrated in the cerebral and coronary circulations (Fabricius & Lauritzen, 1994;Gurevicius et al, 1995). Therefore, we investigated the signi®cance of the endothelium on the hypercapnia-produced relaxation in the mesenteric vascular bed.…”

“…Inhibition of nitric oxide synthase (NOS) attenuates the increase in the cerebral blood¯ow and coronary blood¯ow elicited by hypercapnia (Fabricius & Lauritzen, 1994;Gurevicius et al, 1995). Hsu et al (1995) also demonstrated that hypercapnia stimulates synthesis of vasodilatory prostanoid(s) in cerebral vascular endothelial cells but not in vascular smooth muscle.…”

Effect of changes in pH on wall tension in isolated rat pulmonary artery: role of the RhoA/Rho-kinase pathway

“…Twenty minutes later, the bath solution was returned to control conditions. The response of a preparation to the intervention in these experiments was quantified as the difference between the average tension during minutes [15][16][17][18][19][20] after the switch to experimental conditions and the average steadystate control tension during the last 5 min before the switch. We took samples of the bathing fluid throughout all the experiments for the analysis of PCO2 and pH by using an automated blood-gas analyzer (model 278, Ciba Corning).…”

Effects of acid-base imbalance on vascular reactivity

“…NO was proposed as a mediator of hypercapnia-evoked coronary vasodilation in the in situ dog heart (20) and findings in isolated aortic strips suggest that vasorelaxation in this artery in response to CO 2 may be partially mediated by NO (21). A number of publications have implicated NO in the vasodilatory response of the cerebral vasculature to hypercapnia (22), although more recent evidence suggests that the role of NO may be "permissive" rather than "causative" in this vascular bed (23).…”