Abstract

The aim of the present study was to analyze in spontaneously hypertensive rats of the stroke-prone substrain (SHRSP) the cyclic GMP (cGMP) relaxing system. SHRSP rats (n=15) demonstrated an impaired relaxing response to the NO-donor sodium nitroprusside (SNP) with respect to normotensive Wistar rats (n=15), that was accompanied by a reduction in the level of the main second messenger of NO, cGMP and a reduced expression of the soluble guanylate cyclase (sGC) beta1-subunit determined by Western blot. Doxazosin (10 mg/Kg bw/day for 15 days, n=15) reduced MAP in SHRSP rats. Doxazosin preserved the endothelium-independent relaxation response to SNP in aortic segments from SHRSP rats and increased the expression of the sGC beta1-subunit. In conclusion, independently of the endothelial NO-generating system, endothelial dysfunction also could result from an impaired signalling functionality in vascular smooth muscle cells. Doxazosin-treatment improved the endothelial-independent relaxation and preserved the cGMP generating system in the smooth muscle cell layer.

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