guanosine-diphosphate and Hypertension

GABA(B) receptor function is upregulated in the paraventricular nucleus (PVN) of the hypothalamus in spontaneously hypertensive rats (SHR), but it is unclear whether this upregulation occurs pre- or postsynaptically. We therefore determined pre- and postsynaptic GABA(B) receptor function in retrogradely labeled spinally projecting PVN neurons using whole cell patch-clamp recording in brain slices in SHR and Wistar-Kyoto (WKY) rats. Bath application of the GABA(B) receptor agonist baclofen significantly decreased the spontaneous firing activity of labeled PVN neurons in both SHR and WKY rats. However, the magnitude of reduction in the firing rate was significantly greater in SHR than in WKY rats. Furthermore, baclofen produced larger membrane hyperpolarization and outward currents in labeled PVN neurons in SHR than in WKY rats. The baclofen-induced current was abolished by either including G protein inhibitor GDPbetaS in the pipette solution or bath application of the GABA(B) receptor antagonist in both SHR and WKY rats. Blocking N-methyl-d-aspartic acid receptors had no significant effect on baclofen-elicited outward currents in SHR. In addition, baclofen caused significantly greater inhibition of glutamatergic excitatory postsynaptic currents (EPSCs) in labeled PVN neurons in brain slices from SHR than WKY rats. By contrast, baclofen produced significantly less inhibition of GABAergic inhibitory postsynaptic currents (IPSCs) in labeled PVN neurons in SHR than in WKY rats. Although microinjection of the GABA(B) antagonist into the PVN increases sympathetic vasomotor tone in SHR, the GABA(B) antagonist did not affect EPSCs and IPSCs of the PVN neurons in vitro. These findings suggest that postsynaptic GABA(B) receptor function is upregulated in PVN presympathetic neurons in SHR. Whereas presynaptic GABA(B) receptor control of glutamatergic synaptic inputs is enhanced, presynaptic GABA(B) receptor control of GABAergic inputs in the PVN is attenuated in SHR. Changes in both pre- and postsynaptic GABA(B) receptors in the PVN may contribute to the control of sympathetic outflow in hypertension.

Topics: Animals; Baclofen; Disease Models, Animal; Dose-Response Relationship, Drug; Excitatory Postsynaptic Potentials; GABA Agonists; GABA Antagonists; Glutamine; GTP-Binding Proteins; Guanosine Diphosphate; Hypertension; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Male; Neuronal Plasticity; Paraventricular Hypothalamic Nucleus; Patch-Clamp Techniques; Phosphinic Acids; Presynaptic Terminals; Propanolamines; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Receptors, GABA-B; Staining and Labeling; Sympathetic Nervous System; Synaptic Transmission; Thionucleotides

To investigate the effects of GTP gamma S and GDP beta S on the whole-cell barium currents of voltage-dependent calcium channels (VDC) of the vascular smooth muscle cells (VSMC) from the A4-A5 branches in SHRSP mesenteric artery.. Using the whole-cell Ba2+ current recording of the patch clamp technique.. (1) GTP gamma S, a G-protein agonist, increased whole-cell Ba2+ currents both of SHRSP and Wistar, but SHRSP with a higher ratio of amplitude change than Wistar. In addition, GTP gamma S shifted D infinity to right both in SHRSP and Wistar, but D infinity shifted more in SHRSP than that in Wistar. (2) GDP beta S, a G-protein antagonist, decreased whole-cell Ba2+ currents both of SHRSP and Wistar, but SHRSP with a higher inhibition ratio of amplitude change than Wistar. In addition, GDP beta S shifted F infinity to right and in SHRSP shifted more than control under HP = -80 mV.. The G-protein mechanism may promote Ca2+ influx and contribute to the increase of peripheral resistance during hypertension.

Topics: Animals; Calcium Channels; Cell Separation; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Guanosine Diphosphate; Hypertension; Male; Mesenteric Arteries; Muscle, Smooth, Vascular; Rats; Rats, Inbred SHR; Rats, Wistar; Vascular Resistance