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Effects of Androgens on the Function of Mesenteric Arteries from Normotensive and Hypertensive Rats
Author(s) -
Isidoro Lucía,
Villalpando Diva M.,
Perusquía Mercedes,
Ferrer Mercedes
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.885.5
Subject(s) - sodium nitroprusside , vasodilation , medicine , endocrinology , nitric oxide , vasomotor , mesenteric arteries , calcitonin gene related peptide , dihydrotestosterone , chemistry , vasoconstriction , androgen , stimulation , testosterone (patch) , artery , hormone , neuropeptide , receptor
It has been suggested that androgens may exert cardiovascular protective actions by regulating the release and function of different vascular factors. In addition, increasing attention is paying to testosterone (TES) and its 5‐reduced metabolites, 5α‐ and 5β‐dihydrotestosterone (5α‐ and 5β‐DHT) to induce vasorelaxation in several vascular beds and hypotensive effects in normotensive conscious rats. Interestingly, 5β‐DHT is the most potent vasorelaxant androgen which is genomically inactive. In view of these data, and the lack of studies analyzing the effects of TES, 5α‐ and 5β‐DHT on the function of mesenteric artery from hypertensive rats, the objective of this study was to investigate whether hypertension alters the androgens‐mediated vasorelaxation, as well as their effects on the contractile response induced by electrical field stimulation (EFS); the vasomotor responses induced by the three major released neurotransmitters: noradrenaline (NA), calcitonine gene‐related peptide (CGRP) and nitric oxide were also analyzed. For this purpose, mesenteric artery segments from male Spontaneously Hypertensive rats (SHR) and its normotensive counterparts, Wistar‐Kyoto (WKY) rats, were used to analyze: (i) the concentration‐vasodilator response curve (0.1 μM – 0.1 mM) to TES, 5α‐ and 5β‐DHT; (ii) the effect of androgens (10 nM, incubated for 30 min) on the contractile response induced by EFS (200 mA; 0.3 ms; 1, 2, 4, 8, 16 Hz), and (iii) the vasoconstrictor‐response curve to NA (1 nM–10 μM), and the vasodilator‐response curve to CGRP (1 pM – 0.1 μM) and to the nitric oxide donor, sodium nitroprusside (SNP, 1 pM – 10 μM). The results showed that TES induced a similar relaxation in arteries from SHR or WKY rats, while 5β‐DHT‐induced a greater relaxation in arteries from SHR than those of WKY rats. In arteries from WKY rats, androgens did not modify the EFS‐ or NA‐induced contraction nor the CGRP‐induced relaxation, and only 5β‐DHT increased the SNP‐induced relaxation. In arteries from SHR, androgens unaltered the NA‐induced response, while TES and 5β‐DHT increased the SNP‐induced vasodilation in similar extent. The fact that 5β‐DHT increased the CGRP‐induced vasodilation in a greater extent than TES did, might account for the increased EFS‐induced contraction observed in the presence of TES. These results suggest that 5β‐DHT could be a drug with potential therapeutic benefits for the treatment of hypertension. Support or Funding Information Supported by grants (to M.F.) from the Fondo de Investigaciones Sanitarias (PI1100406), Comunidad de Madrid (S2013/ABI‐2783, “INSPIRA1‐CM”) and Fondo Europeo de Desarrollo Regional.