title: 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.
authors.affiliation: Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Surulere, Nigeria.|Vascular Biology Unit, Centre for Cardiovascular Disease, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Oloyo
authors.affiliation: Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Surulere, Nigeria.
authors.forename: Olusoga A
authors.initials: OA
authors.lastname: Sofola
authors.affiliation: Vascular Biology Unit, Centre for Cardiovascular Disease, College of Pharmacy and Health Sciences, Texas Southern University, Houston, TX, USA.|Department of Environmental and Interdisciplinary Sciences, Texas Southern University, Houston, TX, USA.
authors.forename: Momoh A
authors.initials: MA
authors.lastname: Yakubu
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004326:Drinking / Q000187:drug effects; D006614:Hindlimb / Q000098:blood supply*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D007672:Kidney Cortex / Q000098:blood supply; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D009573:Nitrites / Q000097:blood; D009599:Nitroprusside / Q000494:pharmacology; D009919:Orchiectomy / Q000009:adverse effects*; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013739:Testosterone / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
chemical_list: D009573:Nitrites; D017673:Sodium Chloride, Dietary; D009599:Nitroprusside; D010656:Phenylephrine; D009569:Nitric Oxide; D013739:Testosterone
keywords: acetylcholine; androgens; hind limb perfusion; orchidectomy; salt-induced hypertension; vasorelaxation