Orchidectomy attenuates high‐salt diet‐induced increases in blood pressure, renovascular resistance, and hind limb vascular dysfunction: role of testosterone

Abstract

Sex hormone-dependent vascular reactivity is an underlying factor contributing to sex differences in salt-dependent hypertension. This study evaluated the role of androgens (testosterone) in high salt-induced increase in blood pressure (BP) and altered vascular reactivity in renal blood flow and perfused hind limb preparation. Weanling male rats (8 weeks old, 180-200 g) were bilaterally orchidectomised or sham operated with or without testosterone replacement (Sustanon 250, 10 mg/kg intramuscularly once in 3 weeks) and placed on a normal (0.3%) or high (4.0%) NaCl diet for 6 weeks. The high-salt diet (HSD) increased arterial BP, renal vascular resistance (RVR) and positive fluid balance (FB). These changes were accompanied by decreased plasma nitric oxide levels. The increased BP, RVR and FB observed in the rats fed a HSD were reversed by orchidectomy while testosterone replacement prevented the reversal. Phenylephrine (PE)-induced increased vascular resistance in the perfused hind limb vascular bed was enhanced by HSD, the enhanced vascular resistance was prevented by orchidectomy and testosterone replacement reversed orchidectomy effect. Vasorelaxation responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were impaired in HSD groups, orchidectomy attenuated the impairment, while testosterone replacement prevented the orchidectomy attenuation. These data suggested that eNOS-dependent and independently-mediated pathways were equally affected by HSD in vascular function impairment and this effect is testosterone-dependent in male Sprague-Dawley rats.

l-arginine Supplementation Increased Only Endothelium-Dependent Relaxation in Sprague-Dawley Rats Fed a High-Salt Diet by Enhancing Abdominal Aorta Endothelial Nitric Oxide Synthase Gene Expression

“…Oloyo et al made similar observations in the abdominal aortic rings from SD rats fed a high-salt diet. 6,7 In line with the results of this study, in Dahl saltsensitive hypertensive rats, a high-salt diet was reported to impair endothelium-dependent relaxations induced by a variety of vasodilators. 19,20 This impairment could best be explained by reduced activity and expression of the eNOS mRNA which results in reduced conversion of the substrate, l-arginine present in the plasma to usable nitric oxide to cause vasodilation.…”

“…[21][22][23] Also, previous studies have demonstrated clearly that vascular functions and more importantly endothelium-dependent relaxations are impaired following elevated dietary salt intake in animals and humans. 6,7,24 Many mechanisms have been proposed for this impairment part of which is failure of nitric oxide from the l-arginine-nitric oxide pathway in the endothelium to cause vasodilation 6,24 and alteration in eNOS gene expression.…”

“…The rats were acclimatized for 2 weeks before the commencement of the study. All through the period of the study, depending on the groups, they were either fed with normal rat chow containing 0.3% salt or high-salt diet containing 8% salt (Sofola et al, 2002;Oloyo et al, 2011;Oloyo et al, 2016; Adejare et al, 2017). The rats were housed in transparent cages where they had free access to food and clean water.…”

“…[2][3][4] Vascular function impairment is known to be part of the key mechanisms by which high-salt diet leads to the increase in blood pressure. [5][6][7] In the endothelial cells, endothelial nitric oxide synthase (eNOS) helps in the production of citrulline and nitric oxide from l-arginine. 8 The eNOS mRNA expression has, however, been reported to be a key modulator of vascular tone, and its uncoupling has been shown to contribute to development of hypertension.…”

Protective effect of Xin‑Ji‑Er‑Kang on cardiovascular remodeling in high salt‑induced hypertensive mice

“…Thus, high-salt diet is a major risk factor for the pathogenesis and progression of hypertension in modern society (6). Accumulating evidence indicates that the mechanism of high salt-induced hypertension may include expanded blood volume, increased blood flow and, ultimately, hypertension (7). Furthermore, as numerous studies indicate, high dietary salt intake poses a threat to target organs, increasing the risk of early morbidity and mortality, in addition to its impact on blood pressure, and clinical data also confirm that multiple factors likely contribute to high salt-induced hypertension (2).…”