Hemodynamic responses evoked by endothelin from central cardiovascular neural substrates.
Endothelin-1 (ET-1, 3-10 pmol) applied to the fourth cerebral ventricle of anesthetized ventilated rats decreased mean arterial pressure (MAP, 37 +/- 5 to 55 +/- 5%), heart rate (13 +/- 7 to 21 +/- 3%), and renal blood flow (RBF, 41 +/- 7 to 45 +/- 8%; all values are means +/- SE) for 30-90 min. At a 30-pmol dose of ET-1, the decrease in MAP was preceded by an increase (58 +/- 16%). Micropneumophoresis of ET-1 (100-300 fmol) into discrete glutamate-responsive cardiovascular loci within the nucleus tractus solitarii (NTS), viz., the dorsal strip and the commissural subnucleus, produced depressor and bradycardic responses. However, central ET-1 was ineffective in evoking swallowing responses when microinjected into glutamate-responsive deglutitive sites in the NTS. These data suggest that, at low doses, ET-1 evokes hypotension and bradycardia by a specific neuronal action in the central nervous system; one site of action appears to be the cardiovascular neural substrates within the NTS; decreases in RBF may be secondary to the hypotension, since renal vascular resistance also decreased. In anesthetized nonventilated rats, ET-1 (3 and 10 pmol) applied to the fourth ventricle produced profound respiratory depression accompanied by a transient pressor effect. Thus centrally administered ET-1 can elicit complex cardiovascular responses by a direct action on cardiovascular substrates and/or indirectly via respiratory depression.
Division of Pharmacology, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709.
M A
MA
Hashim
A S
AS
Tadepalli
D000818:Animals; D002320:Cardiovascular Physiological Phenomena; D002490:Central Nervous System / Q000502:physiology*; D003679:Deglutition / Q000502:physiology; D016232:Endothelins / Q000276:immunology / Q000494:pharmacology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006439:Hemodynamics / Q000187:drug effects*; D007106:Immune Sera / Q000276:immunology; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology; D008845:Microinjections; D051381:Rats; D011919:Rats, Inbred Strains; D012121:Respiration, Artificial
D016232:Endothelins; D005971:Glutamates; D007106:Immune Sera; D018698:Glutamic Acid