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 intravenously (i.v.) applied nitric oxide (NO) donor S-nitroso N-acetyl-DL-Penicillamine (SNAP) in conscious spontaneously hypertensive (SHR) to those observed in normotensive Wistar Kyoto (WKY) rats. The study was performed on 7 SHR and 8 WKY instrumented with polyethylene catheters inserted to the abdominal aorta and vena cava for blood pressure (MAP) and heart 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 microM/kg of body weight). The following differences were found between SHR and WKY rats: 1) the threshold dose of SNAP, eliciting significant decrease of MAP was markedly higher in SHR (1.0 microM/kg b.w.) than in WKY (0.2 microM/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 microM/kg b.w. of SNAP and with smaller heart rate acceleration to administration of 10.0, 40.0 and 75.0 microM/kg b.w. of SNAP, 3) in SHR MAP decreased progressively, the greatest decline being observed after administration of the highest dose (75 microM/kg b.w.) of SNAP while in WKY the log dose/delta MAP response curve reached plateau beginning with 2 microM/kg b.w. of SNAP, 4) the slopes and intercepts of the regression lines describing relationship between MAP and HRp after administration of SNAP were significantly different in SHR and WKY rats (P < 0.01). The results indicate that SHR are significantly less sensitive to hypotensive effects of NO generated from moderate doses of SNAP.
Styś
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T
Department of Clinical and Applied Physiology, Warsaw Medical Academy, Poland.
Styś
A
A
Paczwa
P
P
Szczepańska-Sadowska
E
E
Lipkowski
A W
AW
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D007022:Hypotension / Q000139:chemically induced*; D009569:Nitric Oxide; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D026423:S-Nitroso-N-Acetylpenicillamine
D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D010396:Penicillamine