Chronic studies on the interaction between nitric oxide and endothelin in cardiovascular and renal function.

1. Chronic inhibition of nitric oxide synthase (NOS) results in a persistent hypertension, while chronic blockade of endothelin ETA receptors has little effect on arterial pressure. These findings indicate that nitric oxide (NO) plays a more significant role than ET-1 in the long-term maintenance of arterial pressure. 2. Although endothelin (ET) appears to contribute to the hypertension in the early stages of NOS inhibition, blockade of either ETA or both ETA and ETB receptors has only a minor effect on the hypertension beyond the initial 2 weeks of NOS inhibition. 3. Endothelin may play a role in vascular lesion development associated with NOS inhibition, at least within the kidney, which may be related to angiotensin II activity. 4. The processes involved in the hypertension associated with chronic NOS inhibition appear to be dynamic and may include an evolution of ET-1 action. Variability in results from different laboratories may be related to genetic factors and choice of pharmacological agents.