Recovery of erectile function after brief aggressive antihypertensive therapy.
OBJECTIVE
We have previously demonstrated that antihypertensive therapy could structurally modulate blood vessels in the penis, although the impact on erectile function was not established. Given the importance of inadequate penile arterial inflow as a cause of erectile dysfunction we determined in spontaneously hypertensive rats the impact of brief aggressive antihypertensive therapy on structurally based penile vascular resistance, erectile function and mean arterial pressure during and after treatment.


METHODS
Young (15-week-old) and aged (40-week-old) spontaneously hypertensive rats were treated for 2 weeks (enalapril 30 mg./kg. daily plus a low salt diet). Mean arterial pressure was continuously monitored via radio telemetry. Erectile responses were assessed by administering apomorphine (80 microg./kg. subcutaneously) before, during and after treatment. Structurally based vascular resistance was determined in the isolated, perfused penile vasculature 2 weeks after stopping treatment in aged spontaneously hypertensive rats. Certain responses were determined, including resistance at maximum dilatation (lumen size) and at maximum constriction (medial bulk), and EC50 of the alpha-adrenoceptor agonist methoxamine.


RESULTS
In the period after the cessation of drug treatment there was a persistent reduction in the level of arterial pressure (16%) and a doubling of erectile responses compared with pre- treatment. Cardiac and vascular structure regressed, as determined by the mean decrease plus or minus standard deviation in vascular resistance at maximum dilatation (21% +/- 4.5%) and mean reduction in left ventricle mass (10.4% +/- 3.7%). Furthermore, treatment induced a significant right shift in alpha1-adrenoceptor concentration response curve in treated versus control rats (mean EC50 1.09 +/- 0.111 versus 0.76 +/- 0.111).


CONCLUSIONS
The improvement in erectile function after brief aggressive treatment may be related to improvement in structurally based vascular resistance within the penis and the decrease in responsiveness of alpha1-adrenoceptor mediated erectolytic signaling. These findings are suggestive of a new therapeutic strategy for hypertension and erectile dysfunction.
Hale
T M
TM
Department of Pharmacology, Queen's University, Kingston, Ontario, Canada.
Okabe
H
H
Bushfield
T L
TL
Heaton
J P W
JP
Adams
M A
MA
D000818:Animals; D000959:Antihypertensive Agents / Q000633:toxicity*; D001058:Apomorphine / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D004039:Diet, Sodium-Restricted; D004656:Enalapril / Q000633:toxicity*; D008297:Male; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000098:blood supply; D051381:Rats; D011918:Rats, Inbred SHR; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D000959:Antihypertensive Agents; D018340:Receptors, Adrenergic, alpha-1; D004656:Enalapril; D001058:Apomorphine