title: Analysis of erectile responses to H2S donors in the anesthetized rat.
abstract: Hydrogen sulfide (H2S) is a biologically active endogenous gasotransmitter formed in penile tissue that has been shown to relax isolated cavernosal smooth muscle. In the present study, erectile responses to the H2S donors sodium sulfide (Na2S) and sodium hydrosulfide (NaHS) were investigated in the anesthetized rat. Intracavernosal injections of Na2S in doses of 0.03-1 mg/kg increased intracavernosal pressure and transiently decreased mean arterial pressure in a dose-dependent manner. Blood pressure responses to Na2S were rapid in onset and short in duration. Responses to Na2S and NaHS were similar at doses up to 0.3 mg/kg, after which a plateau in the erectile response to NaHS was reached. Increases in intracavernosal pressure in response to Na2S were attenuated by tetraethylammonium (K(+) channel inhibitor) and iberiotoxin (large-conductance Ca(2+)-activated K(+) channel inhibitor), whereas glybenclamide [ATP-sensitive K(+) (KATP) channel inhibitor] and inhibitors of nitric oxide (NO) synthase, cyclooxygenase, and cytochrome P-450 epoxygenase had no effect. These data indicate that erectile responses to Na2S are mediated by a tetraethylammonium- and iberiotoxin-sensitive mechanism and that KATP channels, NO, or arachidonic acid metabolites are not involved. Na2S did not alter erectile responses to sodium nitroprusside (NO donor) or cavernosal nerve stimulation, indicating that neither NO nor cGMP metabolism are altered. Thus, Na2S has erectile activity mediated by large-conductance Ca(2+)-activated K(+) channels. It is suggested that strategies that increase H2S formation in penile tissue may be useful in the treatment of erectile dysfunction when NO bioavailability, KATP channel function, or poor responses to PGE1 are present.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Jupiter
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoo
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Vishwaradh V G
authors.initials: VV
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Edward
authors.affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana.
authors.forename: David J
authors.initials: DJ
authors.lastname: Polhemus
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Taylor C
authors.initials: TC
authors.lastname: Peak
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and.
authors.forename: Prasad
authors.initials: P
authors.lastname: Katakam
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana; and pkadowi@tulane.edu.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000758:Anesthesia; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D054086:KATP Channels / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D010410:Penile Erection / Q000187:drug effects*; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000494:pharmacology
chemical_list: D054086:KATP Channels; D024681:Potassium Channels, Calcium-Activated; D013440:Sulfides; D016718:Arachidonic Acid; D009569:Nitric Oxide; C025451:sodium bisulfide; C033479:sodium sulfide; D006862:Hydrogen Sulfide
keywords: erectile function; hydrogen sulfide; hydrogen sulfide donors; iberiotoxin; tetraethylammonium