Testosterone and Nandrolone Sensitization of Brain Anteroventral Area of Third Ventricle to Hypertonic NaCl-Induced Sympathetic Response

Abstract

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 (ΔV3V) 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. ΔV3V microinjections of (2 µl) 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 µl 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 ΔV3V 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 ΔV3V 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 ΔV3V region to hypertonic NaCl which in turn conducts into a sympathetic vasopressor and heart rate-stimulating action.

Cardiovascular Complications following Chronic Treatment with Cocaine and Testosterone in Adolescent Rats

“…The arterial pressure and HR changes observed in testosterone-treated adolescent animals corroborate previous studies demonstrating that, in adulthood, chronic AAS exposure evokes sustained increases in arterial pressure and resting bradycardia [24], [34], [35]. The arterial pressure elevation is very relevant for cardiovascular function once it has been demonstrated that long-term elevations of as little as 5 mmHg in arterial pressure are associated with an increased risk of stroke and coronary heart diseases [36].…”

Differential Regulation of Aortic Growth in Male and Female Rodents Is Associated With AAA Development

“…Rather than being macrophage-dependent, this change in aortic diameter may be associated with factors, such as blood pressure, which has been shown to be influenced by testosterone [27, 28]. Interestingly, when native males were treated with exogenous testosterone, they had larger body mass and developed AAAs similar to native males (data not shown).…”

Effect of the Single or Combined Administration of Cocaine and Testosterone on Cardiovascular Function and Baroreflex Activity in Unanesthetized Rats

“…14 However, the absence of effects on arterial pressure in animals that received 10-day single administration of testosterone contrasts with previous findings demonstrating that chronic administration of AAS evokes hypertension. 17,27,28 Differences in the treatment time and the AAS used may explain the discrepancy. 17,28 Absence of changes in arterial pressure in cocaine-treated animals corroborates clinical reports that cocaine use is not associated with hypertension in cocaine users.…”

“…17,27,28 Differences in the treatment time and the AAS used may explain the discrepancy. 17,28 Absence of changes in arterial pressure in cocaine-treated animals corroborates clinical reports that cocaine use is not associated with hypertension in cocaine users. 29 However, in vitro studies have demonstrated that AAS is capable of potentiating cardiac and vascular effects of cocaine.…”

“…Chronic administration of either testosterone or cocaine evokes functional changes in activity of brain regions regulating autonomic activity. 28,37 Most of these structures are involved in baroreflex responses, 38 thus suggesting that a central action of testosterone and cocaine could mediate the change in baroreflex activity after repeated administration of these drugs. Direct action of drugs in the heart may also mediate the changes in reflex control of HR.…”