Decreased Response to Vasopressin in the Mesenteric Resistance Arteries of Pregnant Rats: Effects of Nifedipine and Bay K 8644

Abstract

Objective: The purpose of this study was to investigate the contribution of potential-operated calcium (POC) channels in the mechanisms of the blunted effects of vasoconstrictors on mesenteric resistance arteries during normal pregnancy.

Methods: Mesenteric resistance arteries of virgin and term pregnant rats were set up under optimum passive tension in wire myograph systems. Cumulative concentration-response curves of arginine⁸-vasopressin (AVP) were measured in the absence and presence of nifedipine or Bay K 8644, a blocker and an activator, respectively, of POC channels. Binding studies were performed on membrane preparations of the mesenteric vascular bed of both groups of rats using saturation with [³H]nitrendipine.

Results: The maximal response to AVP was statistically similar in the two groups of arteries. Pregnancy shifted the AVP concentration-response curves to the right. nifedipine (1 μmol/L) similarly reduced the maximum response to AVP in arteries of both groups, but produced a larger increase in EC₅₀, the concentration inducing 50% maximum response, in resistance arteries of virgin versus pregnant rats. Bay K 8644 did not affect the maximum tension reached with AVP. However, it increased the effects of small concentrations of AVP in arteries of both groups. This was more important in tissues of virgin than pregnant rats. Binding of [³H]interdipine to membrane preparations of mesenteric vessels was not modified by pregnancy.

Conclusion: Our results suggest a reduced functional influence of POC channels in the myotropic effects of AVP on mesenteric resistance arteries in pregnancy. This decreased influence of POC channels may contribute to resistance of the vasculature to vasopressor agents during pregnancy.