Testosterone and nandrolone sensitization of brain anteroventral area of third ventricle to hypertonic NaCl-induced sympathetic response.
Androgenic steroids increase atherogenesis, thrombogenicity and endothelial dysfunction when administered in high doses, however their effects on NaCl sensitivity of the brain anteroventral area of the third ventricle (DeltaV3V) have not been explored. Sprague-Dawley male rats were anesthetized with sodium pentobarbital (40 mg/kg) and the femoral intra-arterial blood pressure and heart rate monitored through a strain-gauge blood pressure transducer and tachograph. DeltaV3V microinjections of (2 microl) 1.5 mol/l NaCl solution were done according to brain coordinates: AP = 7.0 mm, L = 1.0 mm, D = 7.5 mm through a 0.2-mm diameter stainless steel needle. The injection site was verified with 1.0 microl neutral red solution. Basal systolic blood pressure increased 37.6 and 39.6 mm Hg after testosterone (1 mg/kg/day for 20 days) and nandrolone (1 mg/kg/day for 20 days) treatment respectively; diastolic blood pressure also increased upon testosterone and nandrolone treatment in 36.4 and 53.1 mm Hg, respectively; basal heart rate did not change. Vasopressor response to 1.5 mol/l NaCl DeltaV3V microinjection was higher in testosterone-treated rats; systolic blood pressure increased 56.0 vs. 28.3 control mm Hg; diastolic blood pressure increased 54.0 vs. 25 control mm Hg. This hypertensive response was 29% longer lasting in testosterone compared to vehicle-treated rats. The same pattern of DeltaV3V sensitization to hypertonic NaCl was observed in nandrolone-treated rats. Blood lipid profile changed to a proatherogenic fashion upon testosterone and nandrolone long-term treatment; the plasma-free testosterone concentration increased from 4.9 +/- 0.9 to 36.0 +/-7.1 pg/ml with the same testosterone treatment schedule. In conclusion, long-term androgenic steroid treatment sensitizes the brain DeltaV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.
Rosa
Francisco
F
Departamento de Farmacología, Esc. de Medicina, Universidad de Oriente, Caracas, Venezuela. frankrosa@cantv.net
Antequera
Rafael
R
Vásquez
José
J
Romero-Vecchione
Eduardo
E
Martínez
Angela
A
D000728:Androgens / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D009277:Nandrolone / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012462:Saline Solution, Hypertonic; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013739:Testosterone / Q000008:administration & dosage / Q000494:pharmacology*; D020542:Third Ventricle / Q000187:drug effects; D013997:Time Factors; D014280:Triglycerides / Q000097:blood
D000728:Androgens; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D012462:Saline Solution, Hypertonic; D014280:Triglycerides; D013739:Testosterone; D009277:Nandrolone