Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens

Perusquı́a, Mercedes; Contreras, Daniela; Herrera, Nieves

doi:10.1007/s12020-019-01978-x

Cited by 13 publications

(11 citation statements)

References 47 publications

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“…Androgen therapy of CsX rats with either TES or 5α-DHT at physiological levels beginning at 10 weeks post-CsX completely reversed the HT and restored systolic BP to levels comparable to those of normotensive InT-control male SD rats. These findings are similar to recent reports that castration produced similar levels of HT in both Wistar and Wistar-Kyoto male rats [49] and that in this model, acute iv infusions of TES and its metabolites produced reductions in the HT [50], although this latter study did not examine long-term effects of androgen therapy on the HT. The results of the present study are the first to demonstrate that both endogenous and exogenous TES exert long-term anti-hypertensive effects in male SD rats.…”

Section: Discussionsupporting

confidence: 91%

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

2020

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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.

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Section: Discussionsupporting

confidence: 91%

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

2020

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“…After three 10-min incubation periods, the medium was collected, immediately frozen and stored at -80˚C to measure the basal neurotransmitter release of CGRP or NA. Regarding the determination of NO release, after the stabilization period, the arterial rings were incubated with the specific NO DAF-2 probe (0.5 μM) for 45 min, as previously described [3,7,8]. Once the 500 μL baths were refilled, each with its respective medium, 30-second cumulative EFS periods at 1, 2, 4, 8 and 16 Hz were applied at 1 min intervals, with two parallel platinum electrodes connected to an electro stimulator (Grass, model S44).…”

Section: Analysis Of Neurotransmitters Releasementioning

confidence: 99%

“…It is a well-known fact that male sex steroids are involved in the maintenance of vascular function/structure [1][2][3][4][5][6] and in the regulation of blood pressure [5,7,8]. In addition, epidemiological studies have shown a correlation between low plasma testosterone (TES) levels and hypertension in men [9][10][11][12].…”

Section: Introductionmentioning

confidence: 99%

“…In recent times, more attention is being paid to the 5-dihydroreduced metabolites of TES. Different experimental findings have shown that TES and its 5-reduced dihydrometabolites, 5α-and 5β-dihydrotestosterone (5α-and 5β-DHT), produced an acute non-genomically mediated vasorelaxation of isolated blood vessels [16][17][18] which, in turn, could result in systemic hypotensive effects in vivo [7,8,19].…”

Section: Introductionmentioning

confidence: 99%

“…The mesenteric artery possesses a dense perivascular innervation which releases different neurotransmitters when it is electrically stimulated, such as noradrenaline (NA), nitric oxide (NO) or the calcitonin gene-related peptide (CGRP) [23][24][25][26] which, in turn, they are involved in the regulation of vascular tone. Strikingly, although many studies have analyzed the vasorelaxant and antihypertensive actions of TES, 5α-and 5β-DHT [7,8,18,19], no studies explore in a comparative manner the effect of these androgens on the release and function of the neurotransmitters NO, CGRP and NA in the mesenteric artery of hypertensive rats. Therefore, further research in this respect could contribute to a better understanding of the mechanisms involved in the androgeninduced antihypertensive effect observed in conscious hypertensive rats [7].…”

Section: Introductionmentioning

confidence: 99%

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Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

2021

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Androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, testosterone (TES) and its 5-reduced metabolites, 5α- and 5β-dihydrotestosterone (5α- and 5β-DHT) induce vasorelaxant and hypotensive effects. Furthermore, hypertension has been reported to alter the release and function of the neurotransmitters nitric oxide (NO), calcitonin gene-related peptide (CGRP) and noradrenaline (NA). Since the mesenteric arteries possess a dense perivascular innervation and significantly regulate total peripheral vascular resistance, the objective of this study was to analyze the effect of TES, 5α- and 5β-DHT on the neurogenic release and vasomotor function of NO, CGRP and NA. For this purpose, the superior mesenteric artery from male spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) rats was used to analyze: (i) the effect of androgens (10 nM, incubated for 30 min) on the neurogenic release of NO, CGRP and NA and (ii) the vasoconstrictor-response to NA and the vasodilator responses to the NO donor, sodium nitroprusside (SNP) and exogenous CGRP. The results showed that TES, 5α- or 5β-DHT did not modify the release of NO, CGRP or NA induced by electrical field stimulation (EFS) in the arteries of SHR; however, in the arteries of WKY rats androgens only caused an increase in EFS-induced NO release. Moreover, TES, and especially 5β-DHT, increased the vasodilator response induced by SNP and CGRP in the arteries of SHR. These findings could be contributing to the hypotensive/antihypertensive efficacy of 5β-DHT previously described in conscious SHR and WKY rats, pointing to 5β- DHT as a potential drug for the treatment of hypertension.

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Androgens and Non-Genomic vascular responses in hypertension

Perusquı́a

2022

Biochemical Pharmacology

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Hypotestosteronemia is an important factor for the development of hypertension: elevated blood pressure in orchidectomized conscious rats is reversed by different androgens

Cited by 13 publications

References 47 publications

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

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

Vasomotor action of androgens in the mesenteric artery of hypertensive rats. Role of perivascular innervation

Androgens and Non-Genomic vascular responses in hypertension

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