bq-123 and Erectile-Dysfunction

Endothelin 1 (ET-1) levels and receptors are up-regulated in the erectile tissue of diabetic patients and animal models of erectile dysfunction (ED).. The present study assessed the role of ET-1 receptors in the impaired adrenergic vasoconstriction and nitrergic relaxation of penile arteries from a rat model of insulin resistance.. The effect of ET receptor antagonists was evaluated on the contractile responses to electrical field stimulation (EFS) of penile arteries from obese Zucker rats (OZRs) compared with lean Zucker rats (LZRs). ET receptor expression was determined by immunohistochemistry.. Changes in neural nitrergic relaxation and adrenergic vasoconstriction and the expression of ET receptors in perivascular nerves were assessed.. ET-1 (10(-10)  M) enhanced EFS-induced vasoconstriction, and treatment with the adrenergic neurotoxin guanethidine reduced the contractions induced by ET-1 in penile arteries from both LZRs and OZRs, thus supporting the hypothesis that ET-1 releases noradrenaline from adrenergic nerves. ET-1 antagonized neural nitric oxide (NO)-mediated relaxant responses in LZR arteries, antagonizing relaxations induced by the NO donor S-nitroso-N-acetylpenicillamine to a larger extent in arteries from OZRs. ET(A) and ET(B) receptors were expressed in perivascular fibers colocalized with the neuronal marker protein gene product 9.5 in penile arteries from OZRs. The ET(A) receptor antagonist BQ-123 reversed the enhancing effect of ET-1 on the vasoconstriction elicited by EFS and the ET-1-induced inhibition of nitrergic relaxations in LZRs, restoring them to control levels in penile arteries of OZRs.. ET-1 enhances adrenergic vasoconstriction through presynaptic ET(A) receptors and antagonizes neural NO-mediated relaxation through postsynaptic smooth muscle ET(A) receptors in penile arteries from OZRs, which likely contributes to the augmented vasoconstriction and blunted nitrergic relaxation of erectile tissue under conditions of insulin resistance.

Topics: Adrenergic Agents; Animals; Arteries; Endothelin A Receptor Antagonists; Endothelin-1; Erectile Dysfunction; Guanethidine; Insulin; Insulin Resistance; Male; Muscle Relaxation; Muscle, Smooth, Vascular; Neurotoxins; Nitric Oxide; Obesity; Penile Erection; Penis; Peptides, Cyclic; Rats, Zucker; Receptor, Endothelin A; Vasoconstriction; Vasodilation; Vasodilator Agents

The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 microg/30 microl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.

Topics: Animals; Electric Stimulation; Endothelin Receptor Antagonists; Endothelin-1; Erectile Dysfunction; Injections; Male; Pelvis; Penile Erection; Penis; Peptides, Cyclic; Pressure; Prostate; Radiation Injuries; Radiography; Rats; Rats, Sprague-Dawley; Receptor, Endothelin A; Time Factors