In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving the testicular renin-angiotensin system.

Men are at greater risk of cardiovascular and renal diseases than women. Several hypertensive rat models also exhibit gender differences in blood pressure. Although the mechanisms responsible for these gender differences are not clear, androgens have been shown to promote hypertension. Testosterone is produced by Leydig cells under the regulation of catecholamines acting through both alpha- and beta-adrenoceptors. Some investigators have postulated a putative role of angiotensin II (Ang II) in modulating the action of gonadotropin in Leydig cells, inhibiting testosterone production. In the present work, we analysed the potential mechanism by which the testicular renin-angiotensin system (RAS) decreases the serum circulating levels of testosterone after the in vivo administration of the long-acting selective alpha(1)-adrenergic receptor antagonist doxazosin. RAS was analysed through assessment of the activity of its proteolytic regulatory enzymes. We can conclude that the testicular testosterone production, at least in rat, is regulated by catecholamines through a mechanism involving alpha(1)-adrenergic receptors and RAS, with a putative role for Ang III. Because doxazosin is usually used as a pharmacological therapy in the treatment of hypertension and benign prostatic hyperplasia, our results could also indicate that its benefits are due, at least in part, to decreased serum circulating levels of testosterone.

Effects of alpha1-adrenergic receptor blockade by doxazosin on renin-angiotensin system-regulating aminopeptidase and vasopressin-degrading activities in male and female rat thalamus.

The thalamus has connections with central autonomic centers involved in cardiovascular control and is enervated by noradrenergic fibers. The excitability of thalamic neurons is due to a reduction of ionic currents mediated by alpha(1)-adrenoceptors. The brain renin- angiotensin system (RAS) and the peptide hormone arginine-vasopressin (AVP) are also involved in the central control of blood pressure, and fluid and electrolyte homeostasis. It has been extensively reported that aminopeptidase A (APA), aminopeptidase B (APB), aminopeptidase N (APN), and vasopressin-degrading cystyl aminopeptidase activity (AVP-DA) play an important role in the regulation of the activity of angiotensins and AVP. We have analyzed the effect of alpha(1)-adrenoceptor blockade by doxazosin on RAS-regulating aminopeptidase activities and AVP-DA in soluble and membrane-bound fractions of male and female rat thalamus. Our results show that alpha(1)-adrenoceptors blockade by doxazosin does not modify the RAS through its degrading peptidases at thalamic level either in male or female rats. However, alpha(1)-adrenoceptors blockade shows gender differences in AVP-DA, increasing in males but not in females, supporting an increased capacity of males against females to degrade AVP and, therefore, to regulate cardiovascular homeostasis, under this pharmacological manipulation.