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The effects of intra-arterial infusions of serotonin on internal and external carotid blood flow were determined in anesthetized dogs by electromagnetic flow measurements. Serotonin decreased flow in the internal carotid and increased it in the external carotid. Both responses were blocked by the serotonin antagonist methysergide. The alpha adrenergic antagonist zolertine, the ganglionic blocking agent chlorisondamine and the vasodilator diazoxide blocked external carotid dilator responses but did not modify constriction in the internal carotid. Blockade of external carotid responses by the three drugs was also demonstrated in experiments in which this bed was perfused at a constant rate. These results indicate that the internal and external carotid vascular beds of the dog react in opposite ways to serotonin, that both responses are mediated through the same type of serotonin receptors and that the dilator responses of the external carotid are dependent on vascular tone.

In order to evaluate the relation between hypotension induced by hydralazine and the resultant reflex tachycardia, as well as the role of baroreflex sensitivity in determining the magnitude of these responses, the drug was administered orally at a dose of 1 mg/kg to a group of trained conscious normotensive and renal hypertensive dogs. Responses were assessed by measuring blood pressure and heart rate for 8 hr after dosing and integrating the changes observed over time in order to obtain a mean value. Baroreflex gain was calculated as the ratio of heart rate to blood pressure responses. Hypotension was greater in hypertensives, whereas tachycardia was not different between groups. Gain was therefore smaller in hypertensives, but not uniformly so, a portion of these animals having values within the normotensive range. This high gain group responded with less hypotension and more tachycardia than did the low gain group. Differences in pressure and rate responses to repeated administration of hydralazine between the two groups were minimal. It is suggested that baroreflex gain, an innate individual characteristic, is an important determinant of acute pressure responses to hydralazine in dogs, hypertensive animals having less gain than normotensives and showing increased hypotensive responses. Gain appears not to be as important in determining the chronic effects of the drug.

After the observation that in anesthetized rats the antitubercular agent isoniazid potentiates the hypotensive effect of the vasodilator hydralazine (H) and transforms the accompanying reflex tachycardia to bradycardia, a number of hydrazine (HYD) derivatives were tested for this interaction in pentobarbital-anesthetized rats. All HYDs studied elicited this response in varying degrees, isoniazid, thiosemicarbazide and thiocarbohydrazide being the most active. Experiments were then carried out to explore the possibility of an influence of the HYDs on reflex reactions to H due to interaction with pyridoxal, inhibition of glutamic acid decarboxylase and decreased levels of brain gamma-aminobutyric acid. Although the H-HYDs interaction was prevented by vagotomy, it was unaffected by exogenous pyridoxal, did not occur with the alpha adrenergic antagonist prazosin and was not mimicked by non-HYD pyridoxal reactors. In other experiments, pharmacokinetic interactions and monoamine oxidase inhibition were ruled out as alternative explanations for this phenomenon. It was concluded that the H-HYDs interaction is not related to a possible influence of these drugs on central gamma-aminobutyric acid cardiovascular regulation and that other presently unknown mechanisms are involved.