Hypothalamic and medullary GABAA and GABAB-ergic systems differently regulate sympathetic and cardiovascular systems.
1. To determine whether hypothalamic and medullary GABA (gamma-aminobutyric acid)B stimulation would affect the sympathetic and cardiovascular activities, and to determine whether these effects would be altered in hypertension, baclofen (a GABAB agonist) was injected into a hypothalamic pressor area (ventromedial hypothalamus, VMH), a depressor area (anterior hypothalamus, AH), or a nucleus tractus solitarius (NTS) in normotensive and spontaneously hypertensive rats (SHR). 2. Intracerebroventricular (ICV) injections of a GABAA agonist (muscimol, 1 mu g) decreased blood pressure (BP) and heart rate (HR). ICV injections of baclofen (2 mu g) elicited biphasic depressor and pressor effects, and these effects were abolished by a pretreatment with saclofen (GABAB antagonist, 100 mu g, icv). 3. Muscimol (400 ng) and baclofen (800 ng) injected into VMH decreased sympathetic nerve activity (SNA), BP and HR to almost similar levels, while saclofen injected into VMH increased HR without affecting BP levels. 4. The same dose of baclofen injected into AH increased BP, but muscimol (AH) did not alter BP. 5. Both muscimol and baclofen injected into NTS increased BP, but its magnitude was larger in baclofen injections. 6. Depressor and sympatho-inhibitory effects of baclofen (VMH) in SHR were larger than those in normotensive Wistar-Kyoto (WKY) rats, while pressor responses elicited by baclofen (AH) did not differ between SHR and WKY. 7. In summary, GABA reduces SNA, BP and HR through both GABAA and GABAB receptors in VMH. In addition, the GABAB system acts on AH and NTS to further regulate the cardiovascular activities. In SHR, GABAB-ergic dysfunction in VMH but not in AH might contribute to the development of hypertension.
Takenaka
K
K
Second Department of Medicine, Kyoto Prefectural University of Medicine, Japan.
Sasaki
S
S
Nakamura
K
K
Uchida
A
A
Fujita
H
H
Itoh
H
H
Nakata
T
T
Takeda
K
K
Nakagawa
M
M
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects; D018755:GABA Agonists / Q000008:administration & dosage / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D006439:Hemodynamics / Q000187:drug effects; D007031:Hypothalamus / Q000378:metabolism*; D007276:Injections, Intraventricular; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D009118:Muscimol / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014697:Ventromedial Hypothalamic Nucleus / Q000187:drug effects / Q000502:physiology
D018755:GABA Agonists; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D009118:Muscimol; D001418:Baclofen