Detailed examination of vascular lesions triggered by an inhibitor of endothelium-derived relaxing factor.
BACKGROUND
Inhibition of an endothelium-derived relaxing factor (EDRF) may contribute to the pathogenesis of thrombotic arterial occlusions.


METHODS
We measured the blood pressure and urinary excretion of protein, sodium, and potassium and histologically examined the brains, hearts, and kidneys in normotensive Wistar Kyoto rats (WKY) and stroke-prone spontaneously hypertensive rats (SHRSP) fed on a diet containing: (a) EDRF inhibitor (L-N-nitroarginine:L-NNA); (b) L-arginine, which reverses the effect of L-NNA; or (c) both L-NNA and L-arginine for 1 to 8 weeks. In addition, we examined L-NNA-treated SHRSP, the blood pressures of which were lowered using hydralazine. Furthermore, we produced and examined Goldblatt's renal hypertensive rats, which are of a different type from those resulting from the L-NNA treatment.


RESULTS
Both WKY and SHRSP rats fed on a diet containing L-NNA suffered from hypertension and cerebral infarctions in a dose-dependent manner. Cerebral infarctions occurred whether or not SHRSP rats were treated with an antihypertensive agent when they were fed a high dosage of L-NNA. In contrast, SHRSP rats, treated simultaneously with both L-NNA and L-arginine, suffered few cerebral infarctions, although they were severely hypertensive. In addition, there were no cerebral infarctions in Goldblatt's renal hypertensive rats, although they suffered from advanced hypertension.


CONCLUSIONS
The data indicate that the inhibition of EDRF injures the vessel walls and encourages platelet adhesion to the damaged areas. The adhering platelets narrow the lumen with resultant thrombotic arterial occlusions. Pathophysiologic conditions that decrease EDRF synthesis appear to play an important role in cerebral, renal, and myocardial infarctions.
Department of Internal Medicine, Sanraku Hospital, Tokyo, Japan.
M
M
Tagami
K
K
Ikeda
Y
Y
Nara
H
H
Fujino
A
A
Kubota
F
F
Numano
Y
Y
Yamori
D000818:Animals; D001120:Arginine / Q000009:adverse effects* / Q000031:analogs & derivatives*; D001157:Arterial Occlusive Diseases / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001808:Blood Vessels / Q000473:pathology / Q000648:ultrastructure; D002561:Cerebrovascular Disorders / Q000453:epidemiology / Q000473:pathology / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000494:pharmacology; D006978:Hypertension, Renovascular / Q000473:pathology / Q000503:physiopathology; D015994:Incidence; D008854:Microscopy, Electron; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D019335:Nitroarginine; D011188:Potassium / Q000652:urine; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000652:urine; D013927:Thrombosis / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014652:Vascular Diseases / Q000139:chemically induced* / Q000473:pathology* / Q000503:physiopathology
D019335:Nitroarginine; D006830:Hydralazine; D009569:Nitric Oxide; D001120:Arginine; D012964:Sodium; D011188:Potassium