Phentolamine mesylate relaxes rabbit corpus cavernosum by a nonadrenergic, noncholinergic mechanism.
The contribution of NO-cGMP dependent pathway to phentolamine mesylate-evoked nonadrenergic, noncholinergic relaxation of rabbit corpus cavernosum was investigated in vitro. Stimulation of nonadrenergic, noncholinergic neurons of the rabbit corpus cavernosum elicited frequency-related relaxation that was significantly attenuated by L-NAME (NO synthase inhibitor) or ODQ (an inhibitor of guanylate cyclase). Moreover, tetrodotoxin, a sodium channel blocker, abolished the electrical field stimulation-induced relaxation of rabbit corpus cavernosum, suggesting that neuronal release of NO mediates relaxation to electrical field stimulation. Phentolamine mesylate (30 and 100 nM) dose-dependently enhanced electrical field stimulation-induced relaxation of the rabbit corpus cavernosum. Prazosin (30 microM) and yohimbine (30 microM) failed to affect phentolamine mesylate-mediated nonadrenergic, noncholinergic rabbit penile smooth muscle relaxation, suggesting that phentolamine relaxes rabbit corpus cavernosum independent of alpha-adrenergic receptor blockade. In contrast, pretreatment of the rabbit cavernosal strips with L-NAME significantly-attenuated electrical field stimulation produced relaxations to phentolamine mesylate, suggesting that phentolamine mesylate relaxes rabbit corpus cavernosum by activating NO synthase. The data suggest that phentolamine mesylate relaxes nonadrenergic noncholinergic neurons of the rabbit corpus cavernosum by activating NO synthase and is independent of alpha-adrenergic receptor blockade.
Vemulapalli
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CNS/CV Biological Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Kurowski
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D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000187:drug effects; D004558:Electric Stimulation; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010069:Oxadiazoles / Q000494:pharmacology; D010413:Penis / Q000187:drug effects* / Q000294:innervation; D010646:Phentolamine / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology
C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000317:Adrenergic alpha-Antagonists; D004791:Enzyme Inhibitors; D010069:Oxadiazoles; D011810:Quinoxalines; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D017869:Cyclic GMP-Dependent Protein Kinases; D019331:NG-Nitroarginine Methyl Ester; D010646:Phentolamine