Possible mechanisms of the hypotensive effect of small-to-moderate doses of stonefish venom in rabbits were investigated. Some decrease in blood pressure occurred in the absence of, or prior to, a decrease in force of contraction of the heart, suggesting that peripheral vasodilatation was at least in part responsible for the blood pressure fall after small doses of venom. A decreased force of contraction was associated with the greater decline in blood pressure produced by larger doses of venom. Vasodilatation did not occur in skeletal muscle after intra-arterial injection of venom, and possible effects on other vascular beds were not investigated. Adrenergic blockade was excluded as a mechanism of action of the venom, and evidence of a lack of effect on autonomic ganglionic transmission was obtained. The pressor responses to carotid artery occlusion and anoxia and the depressor responses to central stimulation of the cut right vagus and depressor nerves were unaffected by hypotensive doses of venom.
1. A method of inducing fibrillation in isolated rabbit atria was explored. Atrial fibrillation can be readily produced and maintained under the conditions described by Holland and Burn(2). The method is improved here by the use of much lower concentration of acetylcholine. 2. 1,10-Phenanthroline is as effective as quinidine in stopping induced fibrillation in isolated rabbit atria. 3. 1,10-Phenanthroline, like quinidine, reduces the maximal following rate of isolated rabbit atria, but to a lesser extent. 4. The lowering of maximal following rate by 1,10-Phenanthroline and quinidine can be lessened by reduction of potassium in the medium. 5. At comparable concentrations, 1,10-Phenanthroline does not affect the intrinsic sinus rate of isolated rabbit atria, while quinidine reduces the intrinsic rate markedly. 6. 1,10-Phenanthroline, like quinidine, produces distinct reduction of the rate of depolarization and repolarization of the action potential of the rat atria.
The blood pressure responses to various drugs were investigated in renal hypertensive, cerebral hypertensive and normotensive rabbits. Hexamethonium bromide and Dibenamine reduced the blood pressures of renal and cerebral hypertensives. Effects in the normal were insignificant. The cerebral hypertensive's blood pressure was slightly affected by benzodioxane. Blood pressure was not reduced at all in the other groups. Blood pressure of the renal hypertensive rabbit was greatly reduced by Veriloid and dihydroergocornine. Blood pressures of cerebral and normal animals were affected to a lesser degree. The results suggest that maintenance of hypertension in the cerebral hypertensive rabbit depends on an overactive sympathetic nervous system, possibly due to the release of medullary pressor centers from inhibitory impulses originating in higher centers; whereas, the maintenance of hypertension in the renal hypertensive rabbit may be attributed to an increased reactivity of the peripheral vasculature to a normal sympathetic tone.
Three compounds, 1,10-phenanthroline, tripyridine, and quinidine sulfate, which have potent antifibrillatory actions on isolated rabbit atria, were found to have negative chronotropic and inotropic effects on spontaneously beating rabbit atria. During the first 15–20 min, a progressive decrease in rate was observed with 1,10-phenanthroline and quinidine. A second period of rate decline was noted during which some of the atrial electrical complexes appeared to drop out. This second phenomenon was also noted with tripyridine. High amplification recording showed a splitting of the electrical complex with subsequent sudden losses of portions of the complex. Both tripyridine and quinidine produced apparent atrial standstill. During the standstill, amplification of the electrical recording showed regular electrical activity with the absence of contractions. It is concluded that quinidine and 1,10-phenanthroline affect the S-A node initially to produce atrial slowing; whereas, all three compounds produce a later atrial slowing by junctional blockade, presumably at anatomic junctions such as the region between the S-A node and the atrium, or at the intercalated discs within the atrium proper. The negative inotropic effects of all three compounds are in part explained by this junctional blockade.
