Chronic sildenafil treatment corrects endothelial dysfunction and improves hypertension

American Journal of Nephrology
Keila YaguasBernardo Rodriguez-Iturbe

Abstract

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. 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. 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. These results demonstrate beneficial effects of long-term PDE-5 inhibition in SHR and...Continue Reading

Citations

Oct 26, 2012·American Journal of Physiology. Renal Physiology·Héctor PonsBernardo Rodriguez-Iturbe
Oct 7, 2010·Expert Opinion on Investigational Drugs·Dimitris TousoulisChristodoulos Stefanadis
May 23, 2012·Pharmacology & Therapeutics·Dimitris TousoulisChristodoulos Stefanadis
Nov 21, 2013·The Journal of Sexual Medicine·Biljana MusickiArthur L Burnett
Mar 2, 2012·Kidney & Blood Pressure Research·Edilia TapiaMartha Franco
Jun 2, 2017·Physiological Reviews·Bernardo Rodriguez-IturbeRichard J Johnson
Aug 25, 2020·Hypertension·Ehsan Ataei AtaabadiAnton J M Roks
Apr 4, 2020·Current Pharmaceutical Design·Javier Blanco-Rivero, Fabiano E Xavier

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