Dowell F J, Martin W, Dominiczak A F, Hamilton C A
Clinical Research Initiative, University of Glasgow, UK.
Eur J Pharmacol. 1999 Aug 27;379(2-3):175-82. doi: 10.1016/s0014-2999(99)00511-7.
This study examined both basal and agonist-stimulated effects of nitric oxide in rings of thoracic aorta and carotid artery from 12-week-old stroke-prone spontaneously hypertensive rats (SHRSP) and compared them to those found in rings from normotensive Wistar Kyoto (WKY) controls. Acetylcholine-induced endothelium-dependent relaxation was found to be five-fold more sensitive in both male and female SHRSP when compared with those from age- and sex-matched WKY rats. In contrast, we found a reduction in the effects of basal nitric oxide in the SHRSP rat. Specifically, the ability of basal nitric oxide to depress contractile responses to phenylephrine was found to be reduced in vessels from SHRSP when compared with those from WKY rats. In addition, the endothelium-dependent depression of vasodilator responses to the nitric oxide donor, glyceryl trinitrate, was reduced in vessels from SHRSP when compared to those from WKY rats. Thus, we have shown that the effects of basal nitric oxide are impaired in the SHRSP rat at an age when the effects of agonist-stimulated nitric oxide are actually enhanced. This impairment may be related to the greater susceptibility of basal nitric oxide to destruction by superoxide anion which is known to be produced in excess in this model of hypertension.
