1. [Study on roles of L-arginine to nitric oxide pathway for the cardiovascular control: assessment with a new model of hypertension produced by the chronic administration of nitric oxide synthase inhibitor].
- Author
-
Shudo H
- Subjects
- Animals, Cell Division, Chronic Disease, Disease Models, Animal, Hemodynamics, Hypertension chemically induced, Male, Myocardium pathology, NG-Nitroarginine Methyl Ester, Nitric Oxide Synthase, Norepinephrine metabolism, Rats, Rats, Inbred SHR, Rats, Wistar, Sympathetic Nervous System metabolism, Amino Acid Oxidoreductases antagonists & inhibitors, Arginine analogs & derivatives, Hypertension physiopathology, Nitric Oxide physiology
- Abstract
This study was aimed to make a new stable model of chronic hypertension by administration of a nitric oxide synthase inhibitor. L-Nw-nitroarginine methylester (NAME), and using this model, to investigate the roles of nitric oxide for the cardiovascular regulation. Male Wistar rats were implanted of osmotic pumps filled with saline (control group: n = 8), 0.2M NAME (low NAME group: n = 13) or 1M NAME (high NAME group: n = 12) intraperitoneally. After 4-week observation of blood pressure (BP) and heart rate (HR), blood concentrations of cathecholamine, active renin, L-arginine and L-Nw-nitroarginine were measured and histological changes in aorta and heart were examined. Age-matched SHRSP (n = 9) served as positive controls. BP elevated in the low NAME and high NAME group (113.9 +/- 3.1 to 144.0 +/- 4.4 mmHg, and 114.1 +/- 7.3 to 181.4 +/- 9.0 mmHg, respectively; mean +/- S.E.), while BP remained constant in the control group and SHRSP group (116.8 +/- 5.5 to 120.6 +/- 1.9 mmHg, 200.3 +/- 5.1 to 213.8 +/- 7.4 mmHg, respectively). HR in the low NAME and high NAME group rapidly decreased (not equal to 410 to not equal to 340 bpm) and then slowly returned to the control level. HR in the control group and SHRSP group remained constant (not equal to 420 and not equal to 450 bpm, respectively). Noradrenaline increased significantly in the high NAME group (0.21 +/- 0.03 ng/ml), and there were no significant changes in the control, low NAME and SHR group (0.13 +/- 0.02, 0.14 +/- 0.02, 0.15 +/- 0.03 ng/ml, respectively). Adrenaline, dopamine and active renin concentrations did not differ among 4 groups. Aortic wall/lumen area ratio in the high NAME group was similar to that in SHRSP group, in spite of its lower BP and shorter duration of hypertension compared with SHRSP. Left ventricular wall of the high NAME group was significantly thicker than that of SHRSP group. These findings suggest that, in addition to endothelium-derived NO, NO produced in the brain and peripheral neurons may function to regulate cardiovascular system by inhibiting noradrenaline release from sympathetic nerves or by inhibiting cardiac and vascular cell proliferation.
- Published
- 1994