Hypogonadal hypertension in male Sprague-Dawley rats is renin-angiotensin system-dependent: role of endogenous androgens

Abstract

Background: Acutely, testosterone (TES) and other androgens are efficacious vasodilators, both in vitro and in vivo; however, their long-term effects on arterial blood pressure (BP) remain unclear. It was hypothesized that endogenous androgens exert long-term anti-hypertensive effects on systemic BP through a combination of genomic and nongenomic effects to enhance vasodilation of the systemic vasculature. Methods: The long-term effects of endogenous TES and exogenous TES replacement therapy (TRT) on BP were studied in intact (InT) and castrated (CsX) male Sprague-Dawley (SD) and testicular-feminized male (Tfm, androgen receptor defective) rats (12 weeks old). Systolic BP (tail-cuff plethysmography) was determined weekly for 15 weeks in InT-control and CsX rats. Some CsX-SD rats received androgen replacement therapy at 10-15 weeks with TES-enanthate (TRT; 1.75 mg/kg, 2x/week) or DHT-enanthate (DRT; 1.00 mg/kg. 2x/week) and a separate group of CsX-SD rats received losartanpotassium in drinking water (LST, 250 mg/L) for the entire 15 week period. Expression of renin, angiotensinogen (Agt), angiotensin converting enzyme (ACE), and angiotensin II type I receptor (AT 1 R) mRNA in kidney and aorta were determined by real-time PCR (rt-PCR) and plasma renin levels were determined by radioimmunoassay.

Association between blood and seminal plasma testosterone and aldosterone and their consequences on semen analysis and fertility status in dromedary camel

“…This mechanism occurs via inhibition of aldosterone synthase activity and cytochrome P-450 side-chain cleavage (P450scc) activity, and ACTH-stimulated c-AMP accumulation in the zona glomerulosa cells. Also, endogenous androgens (testosterone) exert anti-hypertensive effects that appear to involve non-genomic and possibly genomic mechanism(s), resulting in reductions in RAS expression in the kidney and enhanced systemic vasodilation in male rats (Hanson et al 2020). Instead, the present study indicated a negative association between blood aldosterone and seminal plasma testosterone in infertile camels.…”

Sex differences in preclinical models of hypertension

“…Interestingly, androgens also appear to have a protective role in this strain. Castrated Sprague-Dawley males exhibited increased blood pressure levels and RAS activity [ 19 ], which supports the role of testosterone in the regulation of the RAS and, consequently, blood pressure. In addition, these changes returned to normal with testosterone treatment [ 19 ].…”

“…Normotensive models Dog ↑ BP in males [14] Fowl ↑ BP and vascular plaque in males [15] WKY rat ↑ BP in males [16] ↑ NO bioavailability in females [17] Sprague-Dawley rat ↑ BP in males ↑ NO bioavailability in females [18] Sex hormones affecting RAS [19] Non-genetic hypertensive models Sprague-Dawley rat (+Ang II infusion)…”

mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

“…Sex hormones play an important role in regulating blood pressure in both men and women ( Jiménez et al 2018 , Hester et al 2019 ). Androgens, especially testosterone, play a key role in cell growth ( Hanson et al 2020 , Stone & Stachenfeld 2020 ). The characteristics of testosterone synthesis and metabolism involve increased protein synthesis, which is essential for normal and hypertrophic growth of cardiomyocytes ( Carbajal-García et al 2020 , Troncoso et al 2021 ).…”