[Doxazosin and soluble guanylate cyclase in a rat model of hypertension].
BACKGROUND
Although different studies have evaluated the ability of endothelial cells to produce NO in the setting of the endothelial dysfunction associated with hypertension, less it is known about the soluble guanylate cyclase system.


OBJECTIVE
To analyze the level of expression of sGC in the vascular wall in Stroke-prone spontaneously hypertensive rats (SHRSP). Moreover, the effect of treatment with an alpha1 adrenergic antagonist, doxazosin, on sGC expression was also evaluated.


METHODS
The study was performed in 24 untreated 20-week-old SPSHR and 12 SPSHR 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 SNP. Doxazosin treatment prevented impaired vasodilatory response to SNP. Expression of the beta1 sGC in the vascular wall of SHRSP determined by Western blot and immunohistochemistry was markedly reduced with respect to that of WKY. Doxazosin treatment increased of beta1 sGC expression in treated SHRSP particularly at the medium level with respect to that of untreated SHRSP.


CONCLUSIONS
SHRSP showed reduced expression of beta1 sGC in the vascular wall and an impaired vasodilator response to SNP which improved with doxazosin treatment. These results suggest the role the sGC system may play in the global treatment of endothelial dysfunction.
Rodríguez-Feo
J A
JA
Laboratorio de Investigación Cardiovascular e Hipertensión. Fundación Jiménez Díaz, Madrid, Spain.
Gómez
J
J
Núñez
A
A
Rico
L
L
Fortes
J
J
de Andrés
R
R
Cabestrero
F
F
Farré
J
J
Casado
S
S
López-Farré
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D017292:Doxazosin / Q000627:therapeutic use*; D006162:Guanylate Cyclase / Q000096:biosynthesis*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D014665:Vasodilator Agents / Q000494:pharmacology
D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; D006162:Guanylate Cyclase; D017292:Doxazosin