Decreased sensitivity of vascular smooth muscle from pregnant rats to phenylephrine may be due to increased Nitric Oxide Synthase activity

Vascular smooth muscle (VSM) from pregnant rats is less sensitive to vasoconstriction by phenylephrine than VSM from nonpregnant rats. We and others have demonstrated this in aortic strips, although the mechanism through which this occurs is unknown. We investigated whether such a decreased response to phenylephrine could be seen in the isolated mesenteric vasculature and whether the response could be potentiated by nitric oxide synthase (NOS) inhibition, since it has been suggested that blood vessels from pregnant rats exhibit increased sensitivity to NO. The mesenteric vasculature was perfused with physiological saline solution to establish baseline perfusion pressure, followed by a constant infusion of phenylephrine (3×10^-5 M). The NOS inhibitor Nω-Nitro-L-arginine (LNNA) was then infused at 3×10^-3 M. As in aorta, phenylephrine produced less vasoconstriction in the mesenteric beds from pregnant rats, perfusion pressure increased 7 mmHg in mesenteric beds from pregnant rats and 32 mmHg in mesenteric beds from nonpregnant rats, (n=3). Addition of LNNA caused a smaller increase in perfusion pressure in mesenteric beds from pregnant rats than nonpregnant rats, 15 vs. 48 mmHg (n=2). These data provide indirect evidence that reduced vasoconstrictor sensitivity in the mesenteric bed of pregnant rats is associated with a greater inhibitory effect of nitric oxide.