Changes in extracellular Ca2+ over a physiologic concentration range differentially modulate reactivity of resistance...

Norepinephrine-induced contractile responses of mesenteric resistance arteries of normotensive Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats were examined in the presence of 1.25, 1.5, and 2.5 mM extracellular Ca2+. In endothelium-intact WKY segments, the three levels of extracellular Ca2+ had no effect on sensitivity to norepinephrine. However, the response of SHR vessels to low dose norepinephrine was significantly enhanced in the presence of 1.25 and 2.5 mM Ca2+ versus 1.5 mM Ca2+. After endothelial WKY vessels responded like SHR vessels, i.e. sensitivity to norepinephrine was enhanced in 1.25 mM Ca2+ compared with 1.5 mM Ca2+. This response to alterations in extracellular Ca2+ was also observed after blockade of the neuronal amine pump with cocaine. These results indicate that vascular smooth muscle of both SHR and WKY respond to small physiologic changes in extracellular Ca2+ with altered sensitivity to norepinephrine. This effect is independent of the neuronal amine pump. We conclude that the endothelium of the normotensive rat protects against Ca(2+)-induced changes in sensitivity to norepinephrine and this protection is absent in SHR.