Moderate hypothermia attenuates α1-adrenoceptor-mediated contraction in human varicose spermatic vein: The role of nitric oxide(Short communication)

Abstract

The effects of moderate hypothermia (28°C) on the response of human varicose spermatic vein to α 1 -adrenoceptor agonist phenylephrine and the role of endothelial nitric oxide (NO) in these effects were studied. Concentrationresponse curves for phenylephrine (10 −9 to 3 × 10 −4 M) were recorded in rings with and without endothelium at 37 and 28°C. To further analyze the role of NO, in the response to phenylephrine during hypothermia, the effects of this agonist in the presence of N G -nitro-L-arginine methyl ester (10 −4 M) were also determined. Under every condition tested, phenylephrine produced a marked, concentration-dependent contraction. Sensitivity of intact veins to the agonist was consistently lower at 28°C than at 37°C. There was no significant difference in phenylephrine response at 28 and 37°C in vessels without endothelium but at 28°C veins without endothelium showed a higher sensitivity than intact veins to phenylephrine. The sensitivity of veins with and without endothelium to nitroprusside (10 −9 to 3 × 10 −3 M) was significantly decreased during hypothermia, and endothelium removal did not affect the relaxation to this nitrovasodilator. These results suggest that moderate hypothermia decreases the sensitivity of human varicose spermatic vein to phenylephrine probably by increasing the availability of endothelial NO.

Nitric oxide-mediated inhibition of phenylephrine-induced contraction in response to hypothermia is partially modulated by endothelial Rho-kinase

“…The PI3K/Akt pathway is involved in endothelial NO production [6,7,22]. Similar to previous studies, the current study found that the PI3K inhibitor wortmannin (10 -7 M) abolished mild hypothermia-induced NO-mediated inhibition of phenylephrine-induced maximal contraction ( Fig.…”

“…7A). As hypothermia causes decreased phenylephrineinduced contraction due to increase NO availability, this L-MANE-induced inhibition of eNOS phosphorylation resulting from combined treatment with phenylephrine and hypothermia seems to be associated with a L-NAME-induced decrease in NO production [4,5,22]. However, the L-NAME-induced increase in eNOS phosphorylation caused by phenylephrine alone at 37°C may be associated with compensatory eNOS activation due to competitive inhibition of L-NAME against L-arginine as a substrate of NO (supplementary Fig.…”

Moderate hypothermia and responses to calcium channel blockers – Role of the nitric oxide

“…Hypothermia has been shown to induce significant changes in responsiveness of vascular smooth muscle cells to various drugs (6,7). Most of the previous studies examining the effect of hypothermia on smooth muscle responses have focused on the effects of cutaneous vessels (13,17,23) and information about non-cutaneous vessels is rather limited. Previously, we investigated the effects of hypothermia on diazoxide-(2) and cilostazol-induced (19) relaxations in calf cardiac vein and coronary artery.…”