Effect of metabolic inhibitors and oxygen on responses of human umbilical arteries

Nair, Xina; Dc, Dyer

doi:10.1152/ajplegacy.1973.225.5.1118

Cited by 12 publications

(5 citation statements)

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“…Under in vivo conditions, O2 supplied by the blood is carried mainly by hemoglobin, whereas in vitro O 2 available in the organ chamber totally depends on physical dissolution. If O2 tension is set at a PO2 of 100 mmHg to mimic the in vivo conditions, the O2 content in the bath solution may be insufficient to sustain normal vasoconstriction (22). Thus, for rings of porcine coronary arteries as used in the present study, the maximal contraction evoked by U-46619 (10 Ϫ6 M) was significantly less when the organ chamber was aerated with 20% O2 (PO2: 140 mmHg) compared with 95% O2 (3.3 Ϯ 1.4 vs. 12.3 Ϯ 1.5 g, n ϭ 7, P Ͻ 0.05).…”

Section: Methodsmentioning

confidence: 99%

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries

Chen

Zhang

Lei

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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. cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries. Am J Physiol Heart Circ Physiol 307: H328 -H336, 2014. First published June 6, 2014; doi:10.1152/ajpheart.00132.2014cGMP is considered the only mediator synthesized by soluble guanylyl cyclase (sGC) in response to nitric oxide (NO). However, purified sGC can synthesize several other cyclic nucleotides, including inosine 3=,5=-cyclic monophosphate (cIMP). The present study was designed to determine the role of cIMP in hypoxic contractions of isolated porcine coronary arteries. Vascular responses were examined by measuring isometric tension. Cyclic nucleotides were assayed by HPLC tandem mass spectroscopy. Rho kinase (ROCK) activity was determined by measuring the phosphorylation of myosin phosphatase target subunit 1 using Western blot analysis and an ELISA kit. The level of cIMP, but not that of cGMP, was elevated by hypoxia in arteries with, but not in those without, endothelium [except if treated with diethylenetriamine (DETA) NONOate]; the increases in cIMP were inhibited by the sGC inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a]quinoxalin-1-one (ODQ). Hypoxia (PO2: 25-30 mmHg) augmented contractions of arteries with and without endothelium if treated with DETA NONOate; these hypoxic contractions were blocked by ODQ. In arteries without endothelium, hypoxic augmentation of contraction was also obtained with exogenous cIMP. In arteries with endothelium, hypoxic augmentation of contraction was further enhanced by inosine 5=-triphosphate, the precursor for cIMP. The augmentation of contraction caused by hypoxia or cIMP was accompanied by increased phosphorylation of myosin phosphatase target subunit 1 at Thr 853 , which was prevented by the ROCK inhibitor Y-27632. ROCK activity in the supernatant of isolated arteries was stimulated by cIMP in a concentration-dependent fashion. These results demonstrate that cIMP synthesized by sGC is the likely mediator of hypoxic augmentation of coronary vasoconstriction, in part by activating ROCK. soluble guanylyl cyclase; inosine 3=,5=-cyclic monophosphate; hypoxic vasoconstriction; endothelium A PREVIOUS STUDY reported that acute hypoxia caused a rapid further increase in tension of contracted canine saphenous veins (31). Subsequent findings demonstrated that such a phenomenon, termed hypoxic augmentation of vasoconstriction (5, 15), occurs in a number of blood vessel types (5,7,8,15,21,23,25,26) contracted with norepinephrine (7, 8), phenylephrine (23), PGF 2␣ (15,25), and the TP receptor agonist U-46619 (21), indicating that it is not unique for a specific vasoconstrictor. It occurs in isolated coronary arteries with but not without endothelium (5,15,25,26). The phenomenon is not affected by bosentan, a blocker of endothelin receptors (5), but is prevented by inhibitors of nitric oxide (NO) synthase (5,15,25). Hypoxic augmentation also occurs in arteries without endothelium treated with an exogenous NO donor (5) However, hypoxic augmentation is not accompanied by changes in the intracellular leve...

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Section: Methodsmentioning

confidence: 99%

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries

Chen

Zhang

Lei

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…(Circ Res 58: 341-347, 1986) THE cellular mechanisms involved in Po 2 -dependent changes in tension in vascular smooth muscle are not understood. The phenomenon has been studied in a variety of different preparations (Carrier et al, 1964;Detar and Bohr, 1968;Fay, 1971;Nair and Dyer, 1973;Clyman et al, 1975;Coburn, 1977;Coburn et al, 1979;Demey and Vanhoutte, 1983). Studies of the nature of the O 2 -sensing reaction and transducing mechanisms between O 2 sensor and contractile proteins in vascular smooth muscle cells may give information about in vivo mechanisms of vasodilation and the general area of O2 chemoreception.…”

Section: From the Department Of Physiology University Of Pennsylvanimentioning

confidence: 99%

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

Coburn¹,

Eppinger²,

Scott³

1986

Circulation Research

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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)

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“…Lowering of catecholamine response produced by cold might induce the elevated receptor response to 5-hydroxytryptamine. The sclerodermatous tissue is poorly oxygenated because of poor circulation, and it has been shown that 5-hydroxytryptamine response in human umbilical arteries has a direct linear relation to PO2 (Nair & Dyer, 1973).…”

Section: Resultsmentioning

confidence: 99%

Hypersensitivity of scleroderma cutaneous vascular smooth muscle to 5-hydroxytryptamine

1976

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Vascular smooth muscle strips from subcutaneous wrist vessels of patients with scleroderma (systemic sclerosis) were studied in an isolated system. No difference between catecholamine response of scleroderma or control vessel strips was observed. Three of four patients demonstrated significant hypersensitivity to 5-hydroxytryptamine as compared to control values. Serotonin hypersensitivity may play a role in the evolution of Raynaud's phenomenon and vascular scleroderma.

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Effect of metabolic inhibitors and oxygen on responses of human umbilical arteries

Cited by 12 publications

References 0 publications

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries

cIMP synthesized by sGC as a mediator of hypoxic contraction of coronary arteries

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

Hypersensitivity of scleroderma cutaneous vascular smooth muscle to 5-hydroxytryptamine

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