Regulation of cardiac sympathetic afferent reflex by GABA(A) and GABA(B) receptors in paraventricular nucleus in rats.
The aim of the present study was to determine the role of GABA(A) and GABA(B) receptors in paraventricular nucleus (PVN) in regulating cardiac sympathetic afferent reflex (CSAR). Under urethane (800 mg/kg) and alpha-chloralose (40 mg/kg) anesthesia, renal sympathetic nerve activity (RSNA), mean arterial pressure (MAP) and heart rate (HR) were recorded in sinoaortic-denervated and cervical-vagotomized rats. CSAR was evaluated based in the response of RSNA to epicardial application of capsaicin (0.3 nmol) or bradykinin (1 nmol). Bilateral PVN microinjection of the GABA(A) receptor agonist isoguvacine (10 nmol) attenuated CSAR, while the GABA(B) receptor agonist baclofen (1 nmol) abolished CSAR. Both isoguvacine and baclofen greatly decreased baseline RSNA and MAP. The GABA(A) receptor antagonist gabazine (0.1 nmol) had no significant effect on CSAR, but the GABA(B) receptor antagonist CGP-35348 (10 nmol) enhanced CSAR. Gabazine caused greater increases in baseline RSNA and MAP than CGP-35348. Vigabatrin (10 nmol), a selective GABA-transaminase inhibitor which increases endogenous GABA level, abolished CSAR, and decreased baseline RSNA, MAP and HR. The effects of vigabatrin were antagonized by combined gabazine (0.1 nmol) and CGP-35348 (10 nmol). The results indicate that activation of either GABA(A) or GABA(B) receptors in the PVN inhibits CSAR, while blockage of GABA(B) receptors in the PVN enhances CSAR. Endogenous GABA in the PVN could have an important role in regulating CSAR.
Departments of Physiology and Biochemical & Molecular Biology, Nanjing Medical University, Nanjing, China.
Ming-Kui
MK
Zhong
Zhen
Z
Shi
Li-Min
LM
Zhou
Juan
J
Gao
Zhao-Hui
ZH
Liao
Wei
W
Wang
Xing-Ya
XY
Gao
Guo-Qing
GQ
Zhu
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001920:Bradykinin / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D006321:Heart / Q000294:innervation*; D007539:Isonicotinic Acids / Q000494:pharmacology; D007668:Kidney / Q000294:innervation; D008297:Male; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D010286:Paraventricular Hypothalamic Nucleus / Q000166:cytology / Q000502:physiology*; D011724:Pyridazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism*; D018080:Receptors, GABA-B / Q000378:metabolism*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D018689:Sensory System Agents / Q000494:pharmacology; D013564:Sympathetic Nervous System / Q000166:cytology / Q000502:physiology*; D020888:Vigabatrin / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D007539:Isonicotinic Acids; D009943:Organophosphorus Compounds; D011724:Pyridazines; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; D018689:Sensory System Agents; C066430:CGP 35348; C049853:gabazine; D020888:Vigabatrin; D001418:Baclofen; D002211:Capsaicin; D001920:Bradykinin; C015300:isoguvacine