Angiotensin-converting enzyme inhibitors and AT1-receptor antagonist restore nitric oxide synthase (NOS) activity and neuronal NOS expression in the adrenal glands of spontaneously hypertensive rats.
During development of hypertension in spontaneously hypertensive (SHR) rats, the activity of adrenal nitric oxide synthase (NOS) was investigated. SHR and Wistar-Kyoto (WKY) rats were studied at different ages: 3-4, 7-8 and 12-13 weeks after birth. Basal NOS activity was measured by the ability of homogenate to convert [3H]-L-arginine to [3H]-L-citrulline. At all ages, SHR rats exhibited 50-60% reduction in NOS activity when compared to age-matched WKY rats. In a following study, SHR rats (12-13 weeks) were treated chronically with the angiotensin I-converting enzyme inhibitors (ACE-I) captopril or enalapril, or the AT1-receptor antagonist losartan (2 x 25, 10 and 60 mg/kg per day for 10 days, respectively). The total NOS activity and protein expression of NOS isoenzymes from adrenals were determined. The basal NOS activity and protein expression of neuronal NOS (nNOS) was significantly increased in treated SHR rats when compared to control rats. The isoforms endothelial NOS and inducible NOS were undetectable. We conclude that impaired NO synthesis in the adrenal glands of SHR rats may contribute to the onset and maintenance of hypertension. The upregulation of nNOS protein in the adrenal glands may be one of the mechanisms by which ACE inhibitors and AT1-receptor antagonists by restoring the NO synthesis, mediate their antihypertensive effects.
Qadri
F
F
Institute for Experimental and Clinical Pharmacology and Toxicology, Medical University of Lübeck, Germany. qadri@medinf.mu-luebeck.de
Arens
T
T
Schwartz
E C
EC
Häuser
W
W
Dominiak
P
P
D000311:Adrenal Glands / Q000187:drug effects* / Q000201:enzymology*; D000375:Aging / Q000187:drug effects / Q000502:physiology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis* / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D013045:Species Specificity
D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; C496322:Nos1 protein, rat