[Ca2+](i) signaling in renal arterial smooth muscle cells of pregnant rat is enhanced during inhibition of NOS

Vascular resistance and arterial pressure are reduced during normal pregnan cy, but dangerously elevated during pregnancy-induced hypertension (PIH), a nd changes in nitric oxide (NO) synthesis have been hypothesized as one pot ential cause. In support of this hypothesis, chronic inhibition of NO synth esis in pregnant rats has been shown to cause significant increases in rena l vascular resistance and hypertension; however, the cellular mechanisms in volved are unclear. We tested the hypothesis that the pregnancy-associated changes in renal vascular resistance reflect changes in contractility and i ntracellular Ca2+ concentration ([Ca2+](i)) of renal arterial smooth muscle . Smooth muscle cells were isolated from renal interlobular arteries of vir gin and pregnant Sprague-Dawley rats untreated or treated with the NO synth ase inhibitor nitro-L-arginine methyl ester (L-NAME; 4 mg.kg(-1).day(-1) fo r 5 days), then loaded with fura 2. In cells of virgin rats incubated in Ha nks' solution (1 mM Ca2+), the basal [Ca2+](i) was 86 +/- 6 nM. Phenylephri ne (Phe, 10(-5) M) caused a transient increase in [Ca2+](i) to 417 +/- 11 n M and maintained an increase to 183 +/- 8 nM and 32 +/- 3% cell contraction . Membrane depolarization by 51 mM KCl, which stimulates Ca2+ entry from th e extracellular space, caused maintained increase in [Ca2+](i) to 292 +/- 1 2 nM and 31 +/- 2% contraction. The maintained Phe- and KCl-induced [Ca2+]( i) and contractions were reduced in pregnant rats but significantly enhance d in pregnant rats treated with L-NAME. Phe- and KCl-induced contraction an d [Ca2+](i) were not significantly different between untreated and L-NAME-t reated virgin rats or between untreated and L-NAME + L-arginine treated pre gnant rats. In Ca2+-free Hanks', application of Phe or caffeine (10 mM), to stimulate Ca2+ release from the intracellular stores, caused a transient i ncrease in [Ca2+](i) and a small cell contraction that were not significant ly different among the different groups. Thus renal interlobular smooth mus cle of normal pregnant rats exhibits reduction in [Ca2+](i) signaling that involves Ca2+ entry from the extracellular space but not Ca2+ release from the intracellular stores. The reduced renal smooth muscle cell contraction and [Ca2+](i) in pregnant rats may explain the decreased renal vascular res istance associated with normal pregnancy, whereas the enhanced cell contrac tion and [Ca2+](i) during inhibition of NO synthesis in pregnant rats may, in part, explain the increased renal vascular resistance associated with PI H.