Enhanced gamma-aminobutyric acid-mediated responses in nucleus tractus solitarius of hypertensive rats.
Previous studies demonstrated that stimulation of type B gamma-aminobutyric acid (GABAB) receptors but not type A (GABAA) receptors in the nucleus tractus solitarius of spontaneously hypertensive rats elicited a larger increase in arterial pressure compared with control rats of the Wistar-Kyoto strain. The present studies extended that observation by examining the cardiovascular response to injection into the nucleus tractus solitarius of a selective GABAB receptor antagonist, CGP 35348, in these strains as well as examining the cardiovascular responses to stimulation or blockade of GABAB receptors in the nucleus tractus solitarius in another model of hypertension, the rat treated with deoxycorticosterone acetate and salt. In both groups of hypertensive rats the pressor response to injection into the nucleus tractus solitarius of the GABA uptake blocking drug nipecotic acid was significantly greater compared with control rats (P < .01 in each model). Similarly, in both models of hypertension, the depressor response elicited by blockade of GABAB receptors in the nucleus tractus solitarius by injection of CGP 35348 was approximately 75% greater compared with control rats (P < .05 in each model). These results suggest that alterations in GABAB-mediated neural transmission in the nucleus tractus solitarius may contribute to the elevated arterial pressure observed in these models of hypertension.
Tsukamoto
K
K
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Sved
A F
AF
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000614:Aminocaproates / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003900:Desoxycorticosterone / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D058788:GABA-B Receptor Antagonists; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009557:Nipecotic Acids / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000494:pharmacology; D011311:Pressoreceptors / Q000187:drug effects / Q000503:physiopathology; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D018080:Receptors, GABA-B / Q000502:physiology*; D012965:Sodium Chloride / Q000494:pharmacology; D017552:Solitary Nucleus / Q000187:drug effects / Q000503:physiopathology*; D020888:Vigabatrin
D000614:Aminocaproates; D058788:GABA-B Receptor Antagonists; D005971:Glutamates; D018377:Neurotransmitter Agents; D009557:Nipecotic Acids; D009943:Organophosphorus Compounds; D018080:Receptors, GABA-B; C030278:nipecotic acid; D018698:Glutamic Acid; D003900:Desoxycorticosterone; D012965:Sodium Chloride; C066430:CGP 35348; D011392:Proline; C010983:homoproline; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin