title: Testosterone reduces vascular relaxation by altering cyclic adenosine monophosphate pathway and potassium channel activation in male Sprague Dawley rats fed a high-salt diet.
abstract: OBJECTIVE
  Male gender and high-salt diet are risk factors for hypertension. The effect of chronic exposure to testosterone is an increase in vascular tone but its influence upon responses induced by other vasoactive agents is not clear. We considered the possibility of interactions between testosterone and a high-salt diet in the mechanisms that are involved in the regulation of vascular tone. Therefore, we designed experiments to assess the involvement of the cyclic adenosine monophosphate (cAMP) pathway and potassium channel activation on vascular relaxation elicited by testosterone deficiency that was induced by orchidectomy in Sprague Dawley rats on a normal or high-salt diet.
  
  
  METHODS
  Weanling male rats were randomly divided into eight groups (n = 6 each) that were either orchidectomized or sham operated with or without testosterone replacement (10 mg/kg body weight of Sustanon 250 intramuscularly, Organon, Holland) and were placed on a normal or high-salt (0.3% or 8% NaCl) diet, respectively, for 6 weeks. Arterial blood pressure was determined before and weekly throughout the experiment using the tail-cuff method. Relaxation responses to forskolin and diazoxide were studied in noradrenaline (0.1 µM) precontracted aortic rings.
  
  
  RESULTS
  There was an increase in the systolic blood pressure of rats placed on a high-salt diet compared with control or orchidectomized rats. Orchidectomy elicited a reduction in the systolic blood pressure while testosterone replacement restored systolic blood pressure to values seen in intact rats. A high-salt diet reduced the relaxation response to forskolin and diazoxide but not in orchidectomized rats while testosterone replacement re-established the blunted relaxation response to forskolin and diazoxide.
  
  
  CONCLUSIONS
  Inhibition of potassium channel or adenylyl cyclase activation appears to contribute to the mechanisms by which a high-salt diet increases vascular tone. These effects were counteracted by orchidectomy in male Sprague Dawley rats.
authors.affiliation: Department of Physiology, Faculty of Basic Medical Sciences, College of Medicine, University of Lagos, Idi-Araba, Lagos, Nigeria. akoloyo@cmul.edu.ng
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Oloyo
authors.forename: Olusoga A
authors.initials: OA
authors.lastname: Sofola
authors.forename: Chikodi N
authors.initials: CN
authors.lastname: Anigbogu
authors.forename: Renuka R
authors.initials: RR
authors.lastname: Nair
authors.forename: Harikrishnan S
authors.initials: HS
authors.lastname: Vijayakumar
authors.forename: Adelaide C
authors.initials: AC
authors.lastname: Fernandez
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology*; D062186:Arterial Pressure; D000242:Cyclic AMP / Q000378:metabolism*; D004195:Disease Models, Animal; D004789:Enzyme Activation; D020536:Enzyme Activators / Q000494:pharmacology; D020249:Hormone Replacement Therapy; D006973:Hypertension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D054086:KATP Channels / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009919:Orchiectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems; D017673:Sodium Chloride, Dietary; D013739:Testosterone / Q000008:administration & dosage / Q000172:deficiency / Q000378:metabolism*; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D020536:Enzyme Activators; D054086:KATP Channels; D017673:Sodium Chloride, Dietary; D014665:Vasodilator Agents; D013739:Testosterone; D000242:Cyclic AMP; D000262:Adenylyl Cyclases