Effects of nitric oxide and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance to nitroglycerin in rats.
The effects of nitric oxide (NO) and noradrenergic activation in the posterior hypothalamus on arterial pressure tolerance induced by subcutaneous injection of nitroglycerin (NTG) was investigated in anesthetized Sprague-Dawley rats. Intravenous injections of NTG (3, 10, and 30 microg/kg) and sodium nitroprusside (1, 3, and 10 microg/kg) produced dose-dependant decreases in arterial blood pressure. Tolerance to NTG was produced by subcutaneous administration of 4.0 mg of NTG as 4 separate hourly injections of 1.0 mg each, affecting the dose-dependent response of NTG IV injection. The 4 high-dose NTG pulse injections produced a marked shift in the dose-response curves for arterial pressure depression induced by intravenous injection of the challenge doses of NTG, but did not alter hypotensive responses to sodium nitroprusside. The tolerance responses to arterial pressure depression were enhanced by a bilateral microinjection of NTG (1 nmol) and by diethylamine NONOate (1 nmol), an NO donor, into the posterior hypothalamus. Bilateral microinjection of guanethidine (1.5 nmol), a noradrenergic blocker, into the posterior hypothalamus inhibits NTG tolerance in a period of time within 2 hours. We conclude that exogenous NO and noradrenergic activation in the posterior hypothalamus play an important role in arterial pressure tolerance to systemically administered NTG.
Guettler
Diane L
DL
Department of Obstetrics, Harbor-University of California Los Angeles Medical Center, David Geffen School of Medicine at University of California at Los Angeles, Torrance, California 90502, USA.
Ma
Sheng-Xing
SX
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D006834:Hydrazines / Q000494:pharmacology; D007034:Hypothalamus, Posterior / Q000378:metabolism; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000008:administration & dosage* / Q000494:pharmacology; D009599:Nitroprusside / Q000009:adverse effects / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000008:administration & dosage* / Q000494:pharmacology
D006834:Hydrazines; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; C084012:1,1-diethyl-2-hydroxy-2-nitrosohydrazine; D005996:Nitroglycerin; D009638:Norepinephrine