Meclofenamate potentiates vasoreactivity to alpha-adrenergic stimulation in chronically hypoxic guinea pigs

Abstract

The aim of this study was to examine the effect of chronic hypoxia on systemic vascular reactivity and the role of prostaglandins in modulating the vascular response to chronic hypoxia. Meclofenamate, a prostaglandin synthesis inhibitor, increased the systemic vascular resistance response to the alpha-adrenergic agonist, phenylephrine, in awake, unrestrained guinea pigs exposed for 6 wk to high altitude (3,900 m), but it did not alter the response in animals kept at low altitude (1,600 m). The systemic vascular resistance response to phenylephrine before treatment with meclofenamate was the same in high- and low-altitude animals. Meclofenamate also increased the contractile response to phenylephrine in aortic rings isolated from high- but not low-altitude animals. The systemic vascular resistance response to angiotensin II was the same in high- and low-altitude animals, and meclofenamate increased this response to the same extent in both groups. Thus chronic hypoxia appeared to enhance vascular production of dilator prostaglandins during beta-adrenergic stimulation.

Renal vasodilatory influence of endogenous carbon monoxide in chronically hypoxic rats

“…*Significant difference from control; #significant difference from normoxic CH rats. conclusion is further supported by several studies demonstrating diminished contractility in isolated vascular preparations from CH rats compared with those from control rats (4,5,8,15).…”

“…Several groups have shown that animals exposed to CH demonstrate diminished responsiveness of the sys- temic vasculature to a variety of vasoconstrictors (5,8,14,15). Furthermore, this attenuated vasoconstriction is maintained even on acute return to a normoxic environment, as previously demonstrated in both conscious animal and isolated vascular ring studies (4,5).…”

“…These data suggest that enhanced HO activity contributes a tonic vasodilatory influence in the renal vasculature of CH rats that may be responsible for the diminished sensitivity to vasoconstrictor agonists observed under these conditions. heme oxygenase; conscious rats; renal blood flow EXPOSURE TO CHRONIC HYPOXIA (CH) results in attenuated vasoconstrictor responses in the systemic vasculature (2,4,5,8,14,15). For example, reduced vascular reactivity has been demonstrated in conscious animals (5,8,14,15) as well as in isolated vascular preparations (2,4,5,8).…”

Adrenergic and vasopressinergic contributions to the cardiovascular response to acute hypoxaemia in the llama fetus

“…Any information available on the effects of chronic hypoxaemia on peripheral vasoreactivity is conflicting. Investigators have reported both increased (Aoki & Robinson, 1969; Harrison et al 1986) and decreased (Doyle & Walker, 1991) peripheral vasoreactivity to α‐adrenergic agonists in the chronically hypoxic rat and guinea‐pig. Information on peripheral vasoreactivity in response to vasoconstrictor/vasodilator agents in either the llama fetus or the chronically hypoxic sheep fetus is not available to date.…”

Effects of Chronic Systemic Hypoxia on Contraction Evoked by Noradrenaline in the Rat Iliac Artery

“…Experiments performed to date indicate that several different mechanisms may underlie this effect and that the mechanisms may vary between vessels taken from different anatomical sites in different species. For example, in uterine arteries of sheep, chronic systemic hypoxia was found to decrease a 1 adrenoreceptor density and agonist binding and to inhibit a 1 adrenoreceptor-contraction coupling , while in guinea-pig aorta, it was reported that chronic hypoxia increased the production of vasodilator prostanoids (Harrison et al 1990). Further, in rat aorta, the attenuated responsiveness to the a 1 adrenoceptor agonist phenylephrine (PE) induced by 48 h of systemic hypoxia was attributed to induction of endothelial haemoxygenase and the consequent enhanced production of the vasodilator, carbon monoxide (Caudill et al 1998).…”