The vasodepressor effect of androgens in pithed rats: potential role of calcium channels.
Estrogens induce vasodilatation and/or hypotension in several experimental models, probably by a blockade of calcium currents. However, very little is known about the potential cardiovascular effects of androgens. We have previously shown that 5 beta-reduced androgens are more potent vasorelaxants than their precursors (delta 4-3 keto), 5-reduced progestins and 17beta-estradiol. The present study set out to investigate if this vasorelaxant effect of 5-reduced androgens is operative in vivo in the analysis of the potential vasodepressor effect of these compounds in vagosympathectomized, pithed rats. After increasing diastolic blood pressure (DBP) by a continuous infusion of norepinephrine (0.059 micromol x kg(-1)min(-1)), i.v. bolus injections of 3 alpha-hydroxy-5 beta-androstan-17-one (etiocholanolone), 5 beta-dihydrotestosterone (5 beta-DHT), and its isomer 5 alpha-dihydrotestosterone (5 alpha-DHT) (5-25 micromol x kg(-1) each) produced, separately, dose-dependent vasodepressor responses. These responses were biphasic: an immediate fall in DBP (reaching the nadir within 1.7 min) was followed by a further slow decrease that reached a maximum between 80 and 100 min after steroid administration. The order of potency of androgens in decreasing DBP was: 5 beta-DHT>5 alpha-DHT=etiocholanolone for the short-lasting response and 5 alpha-DHT>5 beta-DHT>or=etiocholanolone for the longer lasting response. Importantly, the same doses of these compounds produced no significant changes in heart rate. Moreover, 5 beta-DHT significantly antagonized the vasopressor responses to methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluromethylphenyl)-pyridine-5-carboxylate (Bay K 8644) with a blocking profile similar to that of nifedipine (NIF). This finding suggests that a blockade of voltage-operated calcium channels may be involved in androgen-induced hypotension.
Perusquía
Mercedes
M
Universidad Nacional Autónoma de México, Instituto de Investigaciones Biomédicas, Apdo Postal 70-492, 04511México DF, Mexico. perusqui@servidor.unam.mx
Villalón
Carlos M
CM
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D013739:Testosterone / Q000494:pharmacology; D014132:Trachea / Q000601:surgery; D014664:Vasodilation / Q000187:drug effects*
D000728:Androgens; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D013739:Testosterone; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D009638:Norepinephrine