α 1A-adrenoceptors mediate contractions to phenylephrine in rabbit penile arteries

Abstract

Background and purpose: Maintained penile erection depends on the absence of α-adrenoceptor (α-AR) activation and so can be facilitated by α-blockers. This study seeks the α 1-AR subtypes involved in order to inform the pro-erectile consequences of subtype selective blockade. Experimental approach: Wire myography was used with dorsal (nutritional supply) and cavernous (erectile inflow) penile arteries; standard α-AR-selective agonists and antagonists were employed to classify responses. Key results: In both penile arteries noradrenaline (NA) and phenylephrine (PE, α 1-AR agonist) caused concentration-dependent contractions. Sensitivity to NA was increased by NA uptake blockers, cocaine (3 μM) and corticosterone (30 μM). PE responses were antagonised by phentolamine (non-selective α-AR: dorsal pK B 8.00, cavernous 8.33), prazosin (non-subtype-selective α 1-AR: dorsal 8.60, cavernous 8.41) and RS100329 (α 1A-AR selective: dorsal 9.03, cavernous 8.80) but not by BMY7378 (α 1D-AR selective: no effect at 1-100 nM) or Rec15/2615 (α 1B-AR selective: no effect at 1-100 nM). Schild analysis was straightforward in cavernous artery, indicating that PE activates only α 1A-AR. In dorsal artery Schild slopes were low, though α 1A-AR was still indicated. Analysis using UK 14,304 and rauwolscine indicated an α 2-AR component in dorsal artery that may account for low slopes to α 1-AR antagonists. Conclusions and implications: Penile arteries have a predominant, functional α 1-AR population with little evidence of other α 1-AR subtypes. Dorsal arteries (nutritional supply) also have α 1-ARs. Thus, α 1-AR blockers with affinity for α 1A-AR or α 2-AR would potentially have pro-erectile properties; the combination of these perhaps being most effective. This should inform the design of drugs to assist/avoid penile erection. © 2007 Nature Publishing Group. All rights reserved.