Sildenafil And Tadalafil Act At Pericytes To Regulate Vasa Recta Diameter

Abstract

Sildenafil and tadalafil are used clinically for erectile dysfunction [1, 2], yet in addition to their action at sex organs, increasing concentrations of sildenafil citrate have been associated with architectural distortion of kidney vasculature in rats [3], whereas, tadalafil has been reported to provide renoprotective effects against renal ischemic reperfusion injury [4]. Given that it is well established that pericytes regulate vasa recta diameter to regulate medullary blood flow (MBF), we sought to determine whether sildenafil and tadalafil act at pericytes to modulate vasa recta capillary diameter and ultimately MBF. Superfusion of live kidney tissue with sildenafil (20 nM, 40 nM and 80 nM) evoked a significantly greater vasodilation of vasa recta capillaries at pericytes sites (9.10 ± 0.9%, 12.28 ± 1.7% and 25.06 ± 4.4%) than at non-pericyte sites (0.50 ± 0.5%, 1.04 ± 0.3% and 0.95 ± 0.9%; P < 0.01, n=6). Preincubation of tissue with 100 μM L-NNA (nitric oxide synthesis inhibitor) failed to attenuat...