Oxygen-dependent tension in vascular smooth muscle. Does the endothelium play a role?

Abstract

SUMMARY. We investigated a hypothesis that an oxygen sensor involved in hypoxia-induced relaxation of vascular smooth muscle may reside in endothelial cells. We also determined the oxygen dependence of hypoxia-induced decreases in cyclic guanosine 3',5'-monophosphate concentrations in vascular smooth muscle rings. Rings of canine femoral artery, rabbit thoracic aorta, and lamb ductus arteriosus, either with an intact endothelium or with damaged or absent endothelium, were studied using organ baths that allowed changes in Po 2 without a change in pH. Hypoxia-induced relaxations of rabbit thoracic aorta, lamb ductus arteriosus, and canine femoral artery were not dependent on an intact endothelium. The magnitude of hypoxia-induced relaxations was unchanged in rings of canine femoral artery without intact endothelium compared to rings with endothelium. Quasi-steady state organ bath Po 2 -mechanical tension relationships were unchanged in rings of canine femoral artery without endothelium over an organ Po 2 range of 200-20 mm Hg. With rabbit thoracic aorta, magnitudes of hypoxia-induced relaxations were significantly smaller in rings without endothelium. Quasi-steady state plots, where mechanical tension was given as percentage of maximal relaxation, were similar in rings either with or without intact endothelium. Cyclic guanosine 3',5'-monophosphate concentrations were shown to be oxygen-sensitive, decreasing during hypoxia-induced relaxations with a threshold Po 2 of 80-100 mm Hg with canine femoral artery, and 60-80 mm Hg with rabbit thoracic aorta rings, but this finding seems unrelated to the mechanism of hypoxia-induced relaxation. (Circ Res 58: 341-347, 1986)

Involvement of L-Type Calcium Channels in Hypoxic Relaxation of Vascular Smooth Muscle

“…Furthermore, vasodilator metabolites derived from endothelium and parenchymal tissues may exert their relaxant effects by activating K ATP channels on vascular smooth muscle cells [34]. However, our present data, as well as the results of others [8, 10, 11, 33], suggest that vascular smooth muscle itself may be capable of responding to changes in oxygen tension. It may be that vessel size and origin (tissue and species) as well as the experimental methodology employed may account for some of the differences seen regarding oxygen sensing in the vasculature.…”

“…In addition, hypoxia has been reported to stimulate the release of relaxing factors by the endothelium [5, 6, 7]. However, many reports indicate that vascular smooth muscle studied in isolation, in the absence of parenchymal tissues, is capable of relaxing in response to hypoxia [e.g., 8, 9, 10, 11]. Thus, it appears likely that a mechanism inherent to vascular smooth muscle is partially responsible for relaxation in response to hypoxia.…”

Decreased PO₂ and Rabbit Aortic Smooth Muscle Mechanics

“…The simplest explanation to account for a decrease in shortening velocity with a concomitant decrease in MLC phosphorylation levels, as occurred dur ing NE stimulation, is a hypoxia-induced decrease in cel lular Ca2+. Relaxation of NE-stimulated contractions by hypoxia is independent of the endothelium [15], cyclic nucleotide concentrations [16], pi I [17] and probably changes in [Mg2+] [18]. If hypoxia-induced relaxation of an agonist-stimulated contraction is due to a decrease in activator Ca2+ as we suggest, it does not involve receptorphospholipase C coupling mediated by a decrease in GTP concentration [16].…”

Carbon monoxide‐induced relaxation of the ductus arteriosus in the lamb: evidence against the prime role of guanylyl cyclase

“…In addition, this vessel has both prospective targets for the agent, viz. the cytochrome P450/ET-1-based contractile mechanism (Coceani, 1994;Coceani et al, 1996) and the guanylyl cyclase GMP-based relaxing mechanism (Coburn et al, 1986;Walsh & Mentzer, 1987;Coceani et al, 1994). Hence, the ductus appears optimally suited for studying the mechanism of action of CO.…”