Chronic increases in transmural pressure reduce NO-mediated dilations in isolated resistance arteries of the hamster

It is unclear whether the impairment of NO-mediated dilation in hypertensio n is the cause or the consequence of high blood pressure. We therefore stud ied in isolated resistance arteries whether elevated transmural pressure af fects NO-mediated dilation. Arteries (n = 5-7) were perfused at hydrostatic pressures of either 45, 120 or 160 mmHg for 48 h. Subsequently, diameter a nd calcium responses (fura 2) were studied at a transmural pressure of 45 m mHg. Pre-exposure to 120 and 160 mmHg reduced resting diameters and minimal diameters after stimulation with noradrenaline and significantly increased corresponding intracellular free calcium levels in vascular smooth muscle. Moreover, the NO-mediated dilation in response to acetylcholine was signif icantly reduced although the increase in endothelial calcium was not altere d. Dilations induced by the NO donor SNP were not affected. It is concluded that chronically elevated pressure per se impairs endothelial NO productio n by a mechanism distal to receptor-dependent calcium increases.