title: Analysis of erectile responses to bradykinin in the anesthetized rat.
abstract: The kallikrein-kinin system is expressed in the corpus cavernosa, and bradykinin (BK) relaxes isolated corpora cavernosal strips. However, erectile responses to BK in the rat have not been investigated in vivo. In the present study, responses to intracorporal (ic) injections of BK were investigated in the anesthetized rat. BK, in doses of 1-100 μg/kg ic, produced dose-related increases in intracavernosal pressure (ICP) and dose-related deceases in mean arterial pressure (MAP). When decreases in MAP were prevented by intravenous injections of angiotensin II (Ang II), increases in ICP, in response to BK, were enhanced. Increases in ICP, ICP/MAP ratio, and area under the curve and decreases in MAP in response to BK were inhibited by the kinin B2 receptor antagonist HOE-140 and enhanced by the angiotensin-converting enzyme (ACE) inhibitor captopril and by Ang-(1-7). Increases in ICP, in response to BK, were not attenuated by the nitric oxide (NO) synthase inhibitor (N(ω)-nitro-L-arginine methyl ester) or the soluble guanylate cyclase inhibitor (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one) but were attenuated by the cyclooxygenase inhibitor, sodium meclofenamate. Decreases in MAP were not attenuated by either inhibitor. These data suggest that erectile responses are mediated by kinin B2 receptors and modulated by decreases in MAP. These data indicate that ACE is important in the inactivation of BK and that erectile and hypotensive responses are independent of NO in the penis or the systemic vascular bed. Erectile responses to cavernosal nerve stimulation are not altered by BK or HOE-140, suggesting that BK and B2 receptors do not modulate nerve-mediated erectile responses under physiologic conditions. These data suggest that erectile responses to BK are mediated, in part, by the release of cyclooxygenase products.
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Edward
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Edward A
authors.initials: EA
authors.lastname: Pankey
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Jupiter
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: George F
authors.initials: GF
authors.lastname: Lasker
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Daniel
authors.initials: D
authors.lastname: Yoo
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Vishwaradh G
authors.initials: VG
authors.lastname: Reddy
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Taylor C
authors.initials: TC
authors.lastname: Peak
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Insun
authors.initials: I
authors.lastname: Chong
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Jones
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Samuel V
authors.initials: SV
authors.lastname: Feintech
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana.
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Lindsey
authors.affiliation: Department of Pharmacology, Tulane University School of Medicine, New Orleans, Louisiana pkadowi@tulane.edu.
authors.forename: Philip J
authors.initials: PJ
authors.lastname: Kadowitz
mesh_terms: D000758:Anesthesia; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology*; D065094:Bradykinin B2 Receptor Antagonists / Q000494:pharmacology; D002216:Captopril / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D000071756:Soluble Guanylyl Cyclase; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065094:Bradykinin B2 Receptor Antagonists; D018160:Receptors, Cytoplasmic and Nuclear; D014665:Vasodilator Agents; D000804:Angiotensin II; C065679:icatibant; D002216:Captopril; D019001:Nitric Oxide Synthase; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D001920:Bradykinin
keywords: angiotensin-(1–7); angiotensin-converting enzyme; bradykinin; cavernosal nerve stimulation; erectile responses