Alterations In Vascular Functions In Experimental Androgen Deprivation

Abstract

The present work was planned to assess the vascular functions in androgen-deprived state induced by orchidectomy and the mechanisms of control of arterial blood pressure. The study included the assessment of baroreceptor sensitivity and the vascular reactivity of aortic ring smooth muscle to clarify the exact mechanism(s) of vascular dysfunction. Also, androgen deprivation by finasteride treatment was studied for the associated cardiovascular risk factors. I-Androgen-deprived state induced by surgical orchidectomy This was performed on 55 adult male Wistar rats that were classified to orchidectomized rats subjected to androgen deprivation through surgical orchidectomy (ORX, n=28) and their sham-operated controls (n=27). Surgical orchidectomy was achieved by bilateral removal of testes and studied after 4 weeks Surgical orchidectomized rats and their sham-operated controls were subjected to recording of ECG, measurement of arterial blood pressure, and invivo studying of baroreflex functions and their responses to pressor and depressor agents, phenylephrine (PE) and sodium nitroprusside (SNP) respectively. Thereafter, vascular reactivity was studied invitro using isolated aortic rings to determine their contractile and relaxant responses to vasoactive agents, PE and acetylcholine (ACh). Plasma total testosterone, free testosterone and dihydrotestosterone were estimated. In addition, plasma antioxidant catalase (CAT) enzyme activity and the pro-oxidant malondialdhyde (MDA) were measured. Nitrate, the metabolic product of nitric oxide (NO) was assayed in aortic tissue. The results revealed significant reduction in the plasma levels of total testosterone, free testosterone, dihydrotestosterone levels and dihydrotestosterone: testosterone ratio in the orchidectomized rats when compared to their sham-operated controls. This was associated by significant increase in the final body weight, final body mass index and their percentage change in the orchidectomized rats compared to the sham-operated control reflecting the role of testosterone as a potent inhibitor for fat cells to store lipids.