Decreased penile erection in DOCA-salt and stroke prone-spontaneously hypertensive rats

Abstract

Numerous etiological studies have established a positive clinical association between hypertension and erectile dysfunction. However, to date, the mechanism underlying this dysfunction remains to be established. In this study, we demonstrate the presence of erectile dysfunction in two rat models of hypertension, and hypothesize that increased vasoconstrictor signaling via Rhokinase contributes to the decreased erectile response. We found deoxycorticosterone-salt and stroke prone-spontaneously hypertensive rats to exhibit a decreased erectile response, recorded as intracavernosal pressure=mean arterial pressure (ICP=MAP) upon electrical stimulation of the major pelvic ganglion. As previously shown, inhibition of Rho-kinase activity by intracavernosal injection of the selective inhibitor, Y-27632, resulted in an increase in ICP=MAP. However, Y-27632 was significantly less effective at increasing ICP=MAP in the hypertensive as compared to normotensive rats. Additionally, intracavernosal injection of Y-27632 potentiated the voltagestimulated increase in ICP=MAP in both hypertensive and normotensive rats, but was less effective at potentiating the voltage-mediated erectile response in the hypertensive rats. Altogether, our data demonstrate a decreased erectile response in a mineralocorticoid and genetic model of hypertension, and suggest the role of increased cell signaling by Rho-kinase in the vasoconstrictor activity of erectile dysfunction associated with hypertension.

Candesartan cilexetil protects cavernous tissue in spontaneously hypertensive rats

“…Additionally, recent data from DOCA-salt and stroke-prone-spontaneously hypertensive rats have demonstrated a decreased erectile response associated with hypertension. 12 In the last few years, therapeutic intervention against the renin-angiotensin-aldosterone system (RAAS), by both angiotensin I converting enzyme (ACE) inhibitors and more recently through angiotensin II type 1 (AT1) receptor antagonist, has been increasing in acceptance as a useful antihypertensive therapy worldwide. Candesartan cilexetil, a potent, highly selective AT1 receptor antagonist with insurmountable binding properties and slow off-rate from the receptor, has demonstrated to be effective and well tolerated when used in moderate or severe hypertension.…”

The Role Erectile Dysfunction Plays in Cardiovascular Diseases

“…The pathological changes resulting from altered vascular function include injury to the brain, kidney and heart (55). Several studies have established a clinical correlation between incidence of hypertension and ED (58). According to Buccchardt et al, 30% of hypertensive patients have ED and the severity of this sexual disorder is directly proportional to the severity of hypertension.…”

Topical application of a Rho-kinase inhibitor in rats causes penile erection

“…We have previously reported that this same compound lowers blood pressure when high doses are given by intracavernous injection to normal, intact rats 10 or to severely hypertensive rats. 21 Other investigators have reported that oral administration of Y-27632 lowers blood pressure in hypertensive rats but not in normotensive animals. 14 The present study utilizes the castrated rat with 1000 mg Y-27632 applied to the glans penis and surrounding skin.…”