Abstract
The present study was designed to evaluate the contribution of nitric oxide (NO) to regional hemodynamics during the early phase of angiotensin II (Ang II)-induced hypertension. The responses of regional blood flow to chronic NO synthase inhibition with NG-nitro-L-arginine methyl ester (L-NAME) were assessed using radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II-infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean arterial pressure (MAP: 153±4 mmHg) and total peripheral resistance (TPR: 1.61±0.06 mmHg/min/ml), and lower cardiac output (CO: 102±3 ml/min) than vehicle-infused normotensive rats (115±2 mmHg, 0.96±0.05 mmHg/min/ml and 130±7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen, large intestine and skin were significantly reduced in Ang II-infused rats compared with vehicle-infused rats, while those in the lung, heart, liver, kidney, adrenal gland, small intestine, and skeletal muscle were similar. Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days, n=11) resulted in higher MAP (166±6 mmHg) and TPR (1.89±0.18 mmHg/min/ml) and lower CO (87±7 ml/min) than untreated Ang II-infused rats. L-NAME-treated Ang II-infused rats showed widespread increases in regional vascular resistance and reduced blood flow rates in the kidney (3.81±0.27 ml/min/g) and skeletal muscle (0.20±0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88±0.27 and 0.33±0.04 ml/min/g, respectively). However, there were no significant differences in the flow rates of other organs investigated between these animals. An NO donor, (±)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409: 30 μg/kg/min, i.v.), significantly decreased MAP (110±6 mmHg) and TPR (1.23±0.18 mmHg/min/ml) without significant changes in CO (89±9 ml/min) in L-NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood flow rates in the kidney (4.72±0.40 ml/min/g) and skeletal muscle (0.25±0.02 ml/min/g) in these animals. These results suggest that NO counteracts, at least in part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal muscle vascular beds, and is an important modulator in the regulation of blood flow to these organs during the development of Ang II-induced hypertension. (Hypertens Res 2001; 24: 421-427)
