Comparison of endothelin antagonism and angiotensin converting enzyme inhibition on blood pressure and vascular structure in L-NAME-treated SHR.

Spontaneously hypertensive rats (SHR) which receive a nitric oxide synthase inhibitor (L-NAME), develop malignant hypertension, enhanced expression of the endothelin-1 gene in large but not small blood vessels, and elevated plasma renin activity. This study attempted to establish the relative roles of endothelin and renin in L-NAME-treated SHR by comparing the effect of endothelin antagonism and angiotensin converting enzyme inhibition (ACEI) on blood pressure and vascular structure. Adult SHR treated chronically with 30 mg/Kg per day L-NAME were offered the ACEI cilazapril (7.5 mg/Kg per day) or the endothelin receptor antagonist bosentan (100 mg/Kg per day) for 3 weeks. All medication was given orally in the drinking water (L-NAME) or chow (other). Blood pressure was measured by tail-cuff or by an intravascular telemetric method. Small arteries were studied mounted on a wire-myograph. Systolic blood pressure was lowered slightly by cilazapril (213 ± 2.1 vs. 229 ± 1.6 mmHg in untreated SHR-L-NAME, p<0.01) but was not significantly lowered by treatment with bosentan (223 ± 2.1 mmHg). Hypertrophy of aorta segments (weight) and small arteries (media cross-section of coronary, renal, mesenteric and femoral) was significantly (p<0.01) decreased by cilazapril treatment but was unaffected by bosentan. These results suggest that in the absence of endothelin-dependent small artery vascular hypertrophy, endothelin antagonism does not result in lowering of blood pressure. They also may suggest that the renin-angiotensin system plays a role in the malignant form of hypertension found in L-NAME-treated SHR.