Endothelial modulation of norepinephrine-induced constriction of rat aorta at normal and high CO2 tensions

Abstract

Endothelial modulation of norepinephrine (NE)-induced constriction of the isolated rat aorta was studied at normal (PCO2, 41 +/- 0 mmHg) and high CO2 tensions (PCO2, 91 +/- 1 mmHg). In preparations with intact endothelium, increased CO2 tension resulted in rightward shift of the NE dose-response curve with attenuation of maximal contraction. This effect of CO2 was not modified by indomethacin. Treatment with hemoglobin or rubbing of the endothelium meant that increased CO2 tension still resulted in rightward shift of the NE dose-response curve but without altering the maximal contractile response. The basal guanosine 3',5'-cyclic monophosphate (cGMP) levels in control and NE-treated aortic preparations were not affected by increasing the CO2 tension. Thus the inhibitory action of CO2 on NE-induced contraction in the presence of endothelium may not be derived from facilitation of endothelium-derived relaxation factor (EDRF)-induced cGMP synthesis. Increasing the CO2 tension attenuated the sustained contraction induced by the addition of NE and Ca2+ (2.5 mM) to intact endothelium preparations previously bathed in Ca2(+)-free solution. Further addition of Ca2+ (total 5.0 mM) did not increase the contraction. These findings suggest that the intrinsic activity of NE is greatly modified by endothelium at a high CO2 tension. Vasodilation during hypercapnia may be induced at least in part by synergistic actions of EDRF and CO2 on smooth muscle cells.

Effects of acid-base imbalance on vascular reactivity

“…No effect of the NOS inhibitors was observed on basal coronary flow, excluding the role of NO in the regulation of basal coronary vascular tone. This observation conflicts with in vitro findings in guinea pig Langendorff heart preparations, in which NOS inhibition reduced basal coronary vascular flow (21)(22)(23).…”

“…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).…”

Inhibitory effect of ammonium chloride on acetylcholine-induced relaxation.

“…Ten and 20 mmol/L NH,C1 increased resting vascular tone slightly (3,5,10, and 20 mmol/L: not determined, 3±2%, 9±3%, and 13±4% of KC1 contraction) and potentiated norepinephrine contraction (Fig 1). In contrast, 3 and 5 mmol/L NH,C1 did not significantly change resting vascular tone and norepinephrine contraction.…”

“…High CO 2 tension suppressed norepinephrine-induced contraction in rat aorta, possibly with endothelial modulation. 5 Our recent study 8 suggested that acetylcholine relaxation was modified by altered activity of Na + -H + antiport. Thus, NFLjCl-induced impairment of acetylcholine relaxation may be mediated through endothelial function.…”

“…5 Moreover, in a recent study, 8 we altered acetylcholine-induced relaxation by modifying Na + -H + antiport with low Na + medium and amiloride. However, it has not yet been concluded whether pHj change in endothelial cells contributes to the regulation of vascular tone.…”