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A comparative study of the actions of histamine H2 receptor antagonists on transmission in the isolated superior cervical ganglion of the rat.

Ganglionic effects of the histamine H2 receptor antagonists cimetidine, ranitidine and 1-nitro-2-(2-propynylamino)-2-(2-[dimethylaminomethyl-2-furanyl) methylthiol]-ethylamino)ethylene (ORF 17578) were compared in the isolated superior cervical ganglion of the rat. Extracellular recording of compound action potentials showed that the drugs caused concentration-dependent inhibition of ganglionic transmission, as indicated by depression of the postganglionic compound action potential. Cimetidine-induced inhibition of ganglionic transmission was stimulus frequency-dependent. Increasing the Ca2+ from 2.2 to 4.4 mM in the bathing solution did not significantly affect the inhibitory actions of these agents. In the series with ranitidine, pretreatment with DFP to inhibit acetylcholinesterase similarly had no significant effect on the depression of the compound action potential by ranitidine. All three agents had little or no effect on nerve conduction in isolated vagi of the rat. The results indicate that all three histamine H2 receptor blockers inhibited ganglionic transmission, but only in large concentrations. The results also suggest that the blocking effect of these drugs was unrelated to their reported anticholinesterase action or to blockade of histamine H2 receptors, which are believed to exist on the presynaptic membrane. It is suggested that the ganglion effect may be due to the action of these agents on the acetylcholine receptor-ion channel complex in the postsynaptic membrane.

Action Potentials↗

Attenuation of cardiac but not vascular component in baroreflex of spontaneously hypertensive rats.

The cardiac and vascular components of the baroreceptor reflex in spontaneously hypertensive rat (SHR) and stroke-prone spontaneously hypertensive rat (SHRSP) were compared against their counterparts in normotensive Wistar Kyoto rat (WKY). SHR, SHRSP and WKY of 12-16 weeks old were chronically instrumented for intra-arterial recording of blood pressure. Intravenous injections of phenylephrine and nitroprusside were used to challenge their baroreflex. The products of blood pressure change and the half time required for the pressure to return to the control value were used as the quantitative estimation of the blood pressure stabilizing capability. The cardiac component of the baroreflex was obtained from the change in the blood pressure stabilizing capability after blockade of beta and muscarinic receptors by atenolol and atropine, respectively. The vascular component was obtained by subtracting the cardiac component from the total stabilizing capability which was the difference after blockade with a ganglionic transmission blocker, hexamethonium. We found the cardiac component of the baroreflex of the hypertensive rats was significantly less sensitive than that of the WKY. In contrast, the vascular component of the baroreflex of the three strains did not differ significantly. Therefore, we concluded that the 12-16 week old SHRs were able to maintain a stable blood pressure due to the intact vascular component of the baroreflex.

Adrenergic alpha-Agonists↗