EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITION AND ENDOTHELIN ETA RECEPTOR BLOCKADE ON HEMODYNAMICS IN HYPERTENSIVE RATS

1. The objectives of the present study were to study regional differen ces in haemodynamics between spontaneously hypertensive (SHR) and norm otensive Wistar-Kyoto (WKY) rats induced by the nitric oxide synthase (NOS) inhibitor N-G-monomethyl-L-arginine (L-NMMA) and the endothelin ETA receptor antagonist BQ 123 in vivo in tissues known to be importan t for blood pressure (BP) regulation (heart, kidney and skeletal muscl e). Furthermore, the effect of acetylcholine (ACh) infusion (2 mu g/kg per min) was examined after L-NMMA or BQ 123, The microsphere method was used for determinations of cardiac index (CI) and regional haemody namics, 2, N-G-Monomethyl-L-arginine (20 mg/kg) increased BP (26-48%; P<0.01) and reduced CI in both rat strains. BQ 123 (1 mg/kg) reduced B P slightly (-4 to 11%; P<0.05). 3, N-G-Monomethyl-L-arginine significa ntly increased myocardial and skeletal muscle vascular resistance in S HR only; however, in the kidney, L-NMMA reduced blood flow and increas ed vascular resistance in both rat strains. 4. BQ123 induced minor cha nges in regional haemodynamics that were not significantly different b etween the two strains. 5, Acetylcholine following BQ123 induced an in crease in myocardial blood how in WKY rats, but decreased blood flow i n SHR, Acetylcholine following L-NMMA reduced myocardial blood flow in both strains. 6, Acetylcholine following BQ 123 induced renal vasodil ation in WKY rats but, following L-NMMA, ACh did not induce renal vaso dilation in either rat strain. In contrast, L-NMMA did not abolish the vasodilation of acetylcholine in skeletal muscle in WKY rats. 7, In c onclusion, the contribution of nitric oxide to basal vessel tone was n ot impaired in the heart, skeletal muscle and kidney in SHR, Antagonis m of ETA receptors caused similar haemodynamic responses in both rat s trains in these organs. Furthermore, NOS inhibition, but not ETA block ade, blunted the expected ACh-induced vasodilation in the heart and ki dney in WKY rats, but not in skeletal muscle in both strains.