The Vasodilatory Effect of Testosterone on Renal Afferent Arterioles

Background: Sex differences exist in a variety of cardiovascular and renal diseases, and testosterone may contribute to the discrepancy. Afferent arterioles (Af-Arts) are the major resistance vessels in the kidney, and they play an important role in the development of renal injury and hypertension. Objective: We sought to determine the acute effect and underlying mechanism(s) of action of testosterone on Af-Arts. Methods: The mRNA expression of androgen receptors (ARs) in microdissected Af-Arts was measured by reverse transcription-polymerase chain reaction (RT-PCR). An in vitro microperfusion model was used to measure the diameter of Af-Arts in mice. Nitric oxide (NO) was evaluated by an NO-sensitive fluorescent dye, 4-amino-5-methylamino-2',7'-difluorofluorescein diacetate. Results: Testosterone had no effect on microperfused Af-Arts when added to the bath. Therefore, we preconstricted the Af-Arts to approximately 30% with norepinephrine (10(-6) M); administration of testosterone (10(-9)-10(-7) M) subsequently dilated the Af-Arts in a dose-dependent manner (P < 0.001; n = 7). The AR mRNA was expressed in microdissected Af-Arts measured by RT-PCR. An AR antagonist, flutamide (10(-5) M), totally blocked the testosterone (10(-8) M)-induced vasodilator effect. Mean (SEM) NO production of the Af-Art wall was increased when testosterone was added to the bath solution after norepinephrine treatment, from 278.4 (12.1) U/min to 351.2 (33.1) U/min (P < 0.05; n = 3). In the presence of NO inhibition with N-G-nitro-L-arginine methyl ester (3 x 10(-4) M), the testosterone-induced dilatation was blunted compared with norepinephrine (P < 0.05). Conclusions: Testosterone dilated preconstricted mouse Af-Arts in a dose-dependent manner by activation of ARs and partially mediated by NO. (Gend Med. 2012;9:103-111) (C) 2012 Elsevier HS Journals, Inc. All rights reserved.