Doxazosin and soluble guanylate cyclase in a rat model of hypertension

Background. Although different studies have evaluated the ability of endoth elial cells to produce NO in the setting of the endothelial dysfunction ass ociated with hypertension, less it is known about the soluble guanylate cyc lase system. Aim. To analyze the level of expression of sGC in the vascular wall in Stro ke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of t reatment with an alpha (1) adrenergic antagonist, doxazosin, on sGC express ion was also evaluated. Methods. The study was performed in 24 untreated 20-week-old SPSHR and 12 S PSHR treated orally with doxazosin (10 mg/Kg bw/day; for 15 days). A group of normotensive Wistar-Kyoto (WKY) rats were used as controls (n = 12). Results. Isolated aortic segments from SHRSP showed impaired response to SN P. Doxazosin treatment prevented impaired vasodilatory response to SNIP. Ex pression of the beta (1) sGC in the vascular wall of SHRSP determined by We stern blot and immunohistochemistry was markedly reduced with respect to th at of WKY. Doxazosin treatment increased of beta (1) sGC expression in trea ted SHRSP particularly at the medium level with respect to that of untreate d SHRSP. Conclusion. SHRSP showed reduced expression of beta (1) sGC in the vascular wall and an impaired vasoclilator response to SNP which improved with doxa zosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.