Chronic sildenafil treatment corrects endothelial dysfunction and improves hypertension.
BACKGROUND
Nitric oxide (NO) availability plays a critical role in the regulation of blood pressure, endothelial function and arterial structure. Many of the biological actions of NO are mediated by 3'5'-guanosine monophosphate (cGMP), which is rapidly degraded by cGMP phosphodiesterase (PDE). Short-term cardiovascular effects of PDE inhibitors have been studied but the changes resulting from their chronic administration in hypertension have not been evaluated. We investigated if retarding the degradation of cGMP by long-term inhibition of PDE-5 would have beneficial consequences in spontaneously hypertensive rats (SHR), a commonly used experimental model of human essential hypertension.


METHODS
Subgroups of hypertensive 13-week-old male SHR and normotensive Wistar-Kyoto rats were treated with sildenafil, 2.5 mg/kg/day, or vehicle, by gastric gavage for 6 months.


RESULTS
As expected, the untreated SHR had endothelial dysfunction and a steady increment of the blood pressure. In contrast, chronic sildenafil administration reversed endothelial dysfunction, reduced renal oxidative stress and renal macrophage accumulation, and ameliorated the severity of hypertension in SHR.


CONCLUSIONS
These results demonstrate beneficial effects of long-term PDE-5 inhibition in SHR and suggest that its use as an adjunct therapy in essential hypertension should be investigated.
Yaguas
Keila
K
Centro de Investigaciones Biomédicas, Instituto Venezolano de Investigaciones Científicas, Zulia, Venezuela.
Bautista
Rocio
R
Quiroz
Yasmir
Y
Ferrebuz
Atilio
A
Pons
Héctor
H
Franco
Martha
M
Vaziri
Nosratola D
ND
Rodriguez-Iturbe
Bernardo
B
D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000503:physiopathology*; D006973:Hypertension / Q000188:drug therapy*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D010879:Piperazines / Q000008:administration & dosage*; D011687:Purines / Q000008:administration & dosage; D051381:Rats; D011918:Rats, Inbred SHR; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000008:administration & dosage*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D000068677:Sildenafil Citrate