Androgen-mediated induction of the kidney arachidonate hydroxylases is associated with the development of hypertension

Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality, and epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. We show here that treatment of rats with 5-dihydrotestosterone increases the activ...

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Published inAmerican journal of physiology. Regulatory, integrative and comparative physiology Vol. 53; no. 4; pp. R1055 - R1062
Main Authors NAKAGAWA, Kiyoshi, MARJI, Jackleen S, SCHWARTZMAN, Michal L, WATERMAN, Michael R, CAPDEVILA, Jorge H
Format Journal Article
LanguageEnglish
Published Bethesda, MD American Physiological Society 01.04.2003
Subjects
Androgens
Arterial hypertension. Arterial hypotension
Biological and medical sciences
Blood and lymphatic vessels
Cardiology. Vascular system
Experimental diseases
Hypertension
Kidneys
Medical sciences
Hypertension
Renal function
Androgen
Pathophysiology
Rat
androgens
Rodentia
Sex
P-450 eicosanoids
Cardiovascular disease
Male
Biosynthesis
Kidney
HETE
Vertebrata
CYP 4A8
Mammalia
Animal
Hormonal regulation
Blood pressure
Sex steroid hormone
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Summary:Hypertension is a leading cause of cardiovascular, cerebral, and renal disease morbidity and mortality, and epidemiological evidence suggests a role for sex-dependent mechanisms in the pathophysiology of hypertension. We show here that treatment of rats with 5-dihydrotestosterone increases the activity of the kidney arachidonate /-1 hydroxylase and the biosynthesis of 20-HETE (165 and 177% of control untreated male and female rats, respectively) and raises the systolic blood pressures of male and females rats by 46 and 57 mmHg, respectively. These androgen effects are associated with an upregulation in the kidney levels of CYP 4A8 mRNA and a decrease in CYP 4A1 transcripts. Dissected renal microvessels, the target tissue for most of the prohypertensive actions of 20-HETE, show an androgen-dependent upregulation of vascular CYP 4A8 mRNA and a fourfold increase in 20-HETE synthase activity. We propose that androgens regulate renal function and systemic blood pressure through a combination of transcriptional and hemodynamic mechanisms that are ultimately responsible for the regulation of renovascular tone and function. [PUBLICATION ABSTRACT]
ISSN:0363-6119
1522-1490