PERIPHERAL HYPERTENSION AND ALTERATIONS IN PULMONARY VASCULAR REGULATION

We have recently reported in normal isolated-perfused rat lungs that l ow basal tone appears to be regulated by nitric oxide (NO)-dependent a nd -independent mechanisms of soluble guanylate cyclase activation. In this study, we examnined the role of NO in the regulation of pulmonar y artery (PA) tone from rats with renin-dependent hypertension. Rats w ere made hypertensive by ligating the abdominal aorta above the left a nd below the right renal artery (aortic coarctation, AC). Mean arteria l pressure significantly increased from 119 +/- 8.4 mmHg in control an imals to 156 +/- 15 mmHg 7-14 days after AC surgery. PA pressures, how ever, remained unchanged (8.5 +/- 3.4 mmHg in control animals vs. 11 /- 3.3 mmHg in AC animals). Hypoxic contractions in U-46619 precontrac ted isolated small PA (160-260 mu m diameter) were significantly incre ased from 51 +/- 13 mg in the control group to 142 +/- 38 mg (P less t han or equal to 0.05) in AC animals. Nitro-L-arginine (NLA; 100 mu M) contractions were also enhanced in the AC animal. The enhanced NLA res ponse may correlate with an increase in endothelial cell NO synthase ( NOS) as detected by Western blotting (132 +/- 28% of control; P < 0.05 ). These data suggest that, in this renin-dependent model of systemic hypertension, there is increased endothelial cell NOS activity that ma intains low PA tone, preventing the lung from developing increased pre ssures.