Restoration of Female Genital Vasocongestive Arousal Responses in Young and Aged Rats

Authors


Michael A. Adams, PhD, Department of Pharmacology and Toxicology, Queens University, Botterell Hall, Kingston, Ontario, K7L 3N6, Canada. Tel: 613-533-6516; Fax: 613-533-6412; E-mail: michael.adams@queensu.ca

ABSTRACT

Introduction.  Treatments of aged, male hypertensive rats that induce vascular remodeling or that normalize endothelial function are known to produce sustained improvements in erectile function. Whether the treatments targeting these processes benefit female genital vasocongestive arousal (GVA) responses is currently not known.

Aim.  To determine whether the actions of nitric oxide (NO) are critical to the apomorphine (APO)-generated GVA responses in both intact and ovariectomized OVX young adult female rats (before any aging-associated decreases in the responses). In addition, we also investigated whether the diminished GVA responses in aged rats could be restored, at least in part, using an antihypertensive treatment, which is known to enhance erectile responses and improve general vascular function in male rats.

Methods.  In female Wistar rats, APO-induced GVA responses (80 µg/kg, subcutaneously [sc], 30 minutes) were assessed by videomonitoring following various treatments. Young adult females were ovariectomized or were treated with the nitric oxide synthase (NOS) inhibitor N-nitro-L-arginine methyl ester (30 mg/kg, iv), followed by an NO mimetic, sodium nitroprusside (10 µg/kg/minute, intravenous). Aged females (18 months) were treated for 2 weeks with the angiotensin converting enzyme (ACE) inhibitor, enalapril (30 mg/kg/day, orally) plus low sodium (0.04%).

Main Outcome Measures.  APO-induced GVA responses in female rats.

Results.  There was an age-associated reduction in sexual responses in normotensive rats that was greatly enhanced (fourfold) by brief, aggressive antihypertensive treatment. The enhanced vasocongestive responses persisted for a 5-week off-treatment. Both OVX and NOS inhibition significantly decreased sexual responses by approximately 80% in young female rats. Systemic administration of an NO mimetic recovered vasocongestive responses in the NOS-blocked rats, but not in OVX animals.

Conclusions.  Although mechanisms were not established, the major findings were that brief aggressive ACE inhibitor treatment markedly improved sexual responses in aged female rats, and systemic delivery of an NO mimetic recovered sexual responses in globally NOS-blocked animals. Beharry RKS, Hale TM, Heaton JPW, Shamloul R, and Adams MA. Restoration of female genital vasocongestive arousal responses in young and aged rats. J Sex Med 2008;5:804–812.

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