We have previously found that the vascular responsiveness to ₁-adrenergic agonists is reduced in pregnant rats and enhanced in a rat model of pregnancy-induced hypertension produced by chronic treatment of pregnant rats with the nitric oxide (NO) synthase inhibitor N^G-nitro-L-arginine methyl ester (L-NAME). The purpose of this study was to investigate whether the observed changes in vascular reactivity during normal pregnancy and during pregnancy-induced hypertension reflect changes in the mechanisms of Ca²⁺ entry into vascular smooth muscle. ⁴⁵Ca²⁺ influx and active stress during ₁-adrenergic stimulation by phenylephrine and membrane depolarization by 96 mM KCl were measured in deendothelialized aortic strips isolated from virgin and pregnant Sprague-Dawley rats untreated or treated with 1 mg/day L-NAME for 4-6 days and incubated in Krebs solution containing increasing concentrations of extracellular Ca²⁺ ([Ca²⁺]_e). In all groups of rats, both phenylephrine and 96 mM KCl caused [Ca²⁺]_e-dependent increases in active stress and ⁴⁵Ca²⁺ influx. The phenylephrine- and 96 mM KCl-induced active stress and Ca²⁺ influx were significantly reduced in pregnant rats but significantly enhanced in pregnant rats treated with L-NAME. The phenylephrine-induced Ca²⁺ influx-stress relationship was significantly greater than that induced by 96 mM KCl in pregnant rats treated with L-NAME. The phenylephrine-induced Ca²⁺ influx-stress relationship was reduced in pregnant rats but enhanced in pregnant rats treated with L-NAME. Chronic treatment with L-NAME had minimal effect on active stress, Ca²⁺ influx, and the Ca²⁺ influx-stress relationship in virgin rats. These results provide evidence that the mechanisms of Ca²⁺ entry into vascular smooth muscle are inhibited during pregnancy but enhanced during inhibition of NO synthesis in late pregnancy. The enhancement of the phenylephrine-induced Ca²⁺ influx-stress relationship in pregnant rats treated with L-NAME suggests activation of other contractile mechanisms in addition to stimulation of Ca²⁺ entry. These mechanisms appear to be inhibited during normal pregnancy.

arterial pressure; peripheral vascular resistance; calcium; contraction; nitric oxide

This article has been cited by other articles:

				I. Lavelin, N. Meiri, M. Einat, O. Genina, and M. Pines Mechanical strain regulation of the chicken glypican-4 gene expression in the avian eggshell gland Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2002; 283(4): R853 - R861. [Abstract] [Full Text] [PDF]

				R. A. Khalil and J. P. Granger Vascular mechanisms of increased arterial pressure in preeclampsia: lessons from animal models Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R29 - R45. [Abstract] [Full Text] [PDF]

				J. B. Giardina, G. M. Green, K. L. Cockrell, J. P. Granger, and R. A. Khalil TNF-alpha enhances contraction and inhibits endothelial NO-cGMP relaxation in systemic vessels of pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2002; 283(1): R130 - R143. [Abstract] [Full Text] [PDF]

				J. R. Davis, J. B. Giardina, G. M. Green, B. T. Alexander, J. P. Granger, and R. A. Khalil Reduced endothelial NO-cGMP vascular relaxation pathway during TNF-alpha -induced hypertension in pregnant rats Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2002; 282(2): R390 - R399. [Abstract] [Full Text] [PDF]

				J. G. Murphy, J. B. Fleming, K. L. Cockrell, J. P. Granger, and R. A. Khalil [Ca2+]i signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2001; 280(1): R87 - R99. [Abstract] [Full Text] [PDF]

				C. A. Kanashiro, K. L. Cockrell, B. T. Alexander, J. P. Granger, and R. A. Khalil Pregnancy-associated reduction in vascular protein kinase C activity rebounds during inhibition of NO synthesis Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2000; 278(2): R295 - R303. [Abstract] [Full Text] [PDF]