Further studies on central actions of nitroglycerin and lack of evidence for nitroglycerin interacting on [3H]clonidine binding sites in cortex membranes.
Decerebration and transection of the spinal cord totally abolished the hypotensive and tachycardiac responses to i.c.v injection of nitroglycerin (NTG) and reduced the tachycardia induced by i.v. injection of the drug. The hypotensive responses to i.v. injection of sodium nitroprusside were not altered by decerebration. Microinjection of NTG (0.1-1.0 nmol) into anterior hypothalamic medial preoptic area (AH/POA) produced dose-dependent decreases in mean arterial pressure and heart rate, but minimal responses were induced when the same doses of NTG were injected into the rostral ventrolateral medulla. Pretreatment with rauwolscine (2.5 nmol), injected into the AH/POAs, antagonized the depressor responses to NTG when it was administered into the areas or given i.v. However, rauwolscine did not alter the depressor responses induced by i.v. sodium nitroprusside. Prazosin (1.5 nmol) in the AH/POA did not alter the bradycardic effects induced by microinjection of NTG into the areas. (minus)-Epinephrine significantly interacted with alpha-2 adrenoceptor binding sites, but serotonin and NTG did not interact with [3H] clonidine binding sites in cortex membranes. Results suggest that cardiovascular responses after i.v. injection of NTG involve central and peripheral component. AH/POA is one of the central sites involved in the depressor effects of NTG. NTG-induced modulation of noradrenergic transmission appears to stimulate alpha-2 adrenoceptors in the central nervous system, but the drug does not involve direct interaction with alpha-2 adrenoceptors. Hypotensive effects of sodium nitroprusside result from its action at peripheral sites.
Ma
S
S
Department of Pharmacology, College of Medicine, University of Iowa, Iowa City.
Long
J P
JP
Bhatnagar
R K
RK
D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism*; D003655:Decerebrate State / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism
D011942:Receptors, Adrenergic, alpha; D005996:Nitroglycerin; D003000:Clonidine