Effects of antihypertensive drugs on nitric oxide synthase activity in rat kidney.
Nitric oxide production has been reported to be reduced in hypertensive patients. In this study, we investigated the effects of antihypertensive drugs such as calcium channel blocker, amlodipine, alpha 1-adrenoceptor blocker, doxazosin and angiotensin converting enzyme (ACE) inhibitor, imidapril on nitric oxide synthase (NOS) activity in the kidneys of L-NAME-induced hypertensive rats. An increased blood pressure in L-NAME-induced hypertensive rats was significantly decreased by these antihypertensives to the same extent at four weeks. Nitrite production from the kidney slices was significantly suppressed in L-NAME-induced hypertensive rats. This suppression of nitrite production was reversed to the control level in the rats treated with amlodipine, and significantly enhanced by doxazosin and imidapril. Immunoreactivity for both the brain-type NOS in the macula densa and endothelial cell-type NOS in renal vasculature was diminished in L-NAME rats, and antihypertensive therapies, especially doxazosin and imidapril, increased NOS immunostaining. The increased glomerulosclerosis score in the L-NAME group was significantly lowered by the treatment with doxazosin and imidapril. In conclusion, a decreased NOS activity in L-NAME-induced hypertensive rats was significantly increased by alpha 1-adrenoceptor blockers and ACE inhibitors in the kidney, and this increased NOS activity may have a role in the prevention of glomerulosclerosis.
Tojo
A
A
Second Department of Internal Medicine, University of Tokyo, Japan.
Kobayashi
N
N
Kimura
K
K
Hirata
Y
Y
Matsuoka
H
H
Yagi
S
S
Omata
M
M
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000503:physiopathology; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D000317:Adrenergic alpha-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester