Endothelium-dependent and -independent relaxations in aortic rings obtained from hypertensive hooded (Aguti) rats.

Abstract

Experimental hypertension studies are few in the hooded (Aguti) rat. The present study was designed to investigate the usefulness of this rat strain for experimental hypertension studies and to test the hypothesis that the hypertension may be associated with a diminution of endothelium dependent and independent relaxations. Hypertension was induced in inbred hooded rats (n=8 each) by administering 8% salt in the diet and /or 100 mg/kg/day Nω-nitro-L-arginine-methyl-ester (LNAME) in the drinking water for six and/or four weeks respectively. The rats were anaesthetized using a 25% urethane and 1% chloralose mixture given intraperitoneally at a dose of 5mg/kg. Their blood pressure was measured invasively. Thereafter, relaxations of rat aortic preparations to acetylcholine, histamine and sodium nitroprusside (SNP) were assessed using standard organ bath conditions. P<0.05 was taken as statistically significant. The mean arterial pressure (MAP;mm Hg) rose significantly in all test groups (Salt: 148.3±4.6; L-NAME: 181.7±8.3; Salt+L-NAME:154.9±8.7) compared with control (94.2±6.8; P<0.05). The MAP was significantly (P<0.05) higher in the L-NAME group than in all the other groups. The heart rate fell significantly in the salt + L-NAME group compared to control (P<0.05).The IC50 of acetylcholine in aortic rings from L-NAME rats (7.9 x 10-1 ± 6.0 x 10- 3) was significantly higher than in rings from control (9.4 x 10-8 ± 2.8 x 10-8), salt (7.8 x 10-7 ± 4.7 x
10-7) and salt + L-NAME (3.3 x 10-7 ± 2.1 x 10-7) rats (P<0.05). The IC50 of histamine and SNP in the rings from the test groups of rats showed no significant difference from control. These results suggest
that the hooded rat may be useful for experimental hypertension studies. Also, endothelium dependent and independent relaxations were preserved in the various forms of hypertension studied except in chronic NOS inhibition where the former was attenuated in response to acetylcholine.