DECREASED HYPOTENSIVE RESPONSIVENESS TO NITRIC-OXIDE DONOR S-NITROSO N-ACETYL-DL-PENICILLAMINE (SNAP) IN SPONTANEOUSLY HYPERTENSIVE (SHR) RATS

The aim of the study was to compare hemodynamic effects of intravenous ly (i.v.) applied nitric oxide (NO) donor S-nitroso N-acetyl-DL-Penici llamine (SNAP) in conscious spontaneously hypertensive (SHR) to those observed in normotensive Wister Kyoto (WKY) rats. The study was perfor med on 7 SHR and 8 WKY instrumented with polyethylene catheters insert ed to the abdominal aorta and vena cava for blood pressure (MAP) and h eart rate period (HRp) monitoring, and for i.v. administration of SNAP (0.05, 0.1, 0.2, 0.5, 1.0, 2.0, 5.0, 10.0, 20.0, 40.0 and 75.0 mu M/k g of body weight). The following differences were found between SHR an d WKY rats: 1) the threshold dose of SNAP, eliciting significant decre ase of MAP was markedly higher in SHR (1.0 mu M/kg b.w.) than in WKY ( 0.2 mu M/kg b.w.), 2) SHR responded with significantly smaller maximum decreases of MAP to administration of 1.0, 2.0, 5.0 and 10.0 mu M/kg b.w. of SNAP and with smaller heart rate acceleration to administratio n of 10.0, 40.0 and 75.0 mu M/kg b.w. of SNAP, 3) in SHR MAP decreased progressively, the greatest decline bring observed after administrati on of the highest dose (75 mu M/kg b.w.) of SNAP while in WKY the log dose/Delta MAP response curve reached plateau beginning with 2 mu M/kg b.w, of SNAP, 4) the slopes and intercepts of the regression lines de scribing relationship between MAP and HRp after administration of SNAP were significantly different in SHR and WKY rats (P < 0.01). The resu lts indicate that SHR are significantly less sensitive to hypotensive effects of NO generated from moderate doses of SNAP.