Interference by mepacrine with the storage of 5-hydroxytryptamine in blood platelets.
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Biomedical subjects
Publications and source records attributed to G B Picotti.
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The adrenal responses in calves submitted to simulated transport on three occasions for 30 min were evaluated. Plasma adrenaline, cortisol and NEFA increased significantly during simulated transport but became less marked in successive trials. Haematological stress-related parameters (Hb, PCV) increased to the same extent on repeated exposure to simulated transport. Plasma noradrenaline, glucose and cholesterol values were unchanged throughout the study.
Histamine (H) is stored in man in the cardiovascular as well as in other systems, from where it can be released under exposure to immunologic and nonimmunologic stimuli. To understand better the hemodynamic changes produced in man by endogenous H release, we infused H for 3.5-7 min at the rate of 0.4 microgram/kg/min i.v. in four patients with normal left ventricular (LV) function undergoing diagnostic cardiac catheterization. We observed a significant fall in systolic, diastolic, and mean aortic pressure, systemic vascular resistance, LV end-diastolic pressure, and stroke index, and a significant rise in heart rate, cardiac output, and LV dP/dtmax, with small changes in mean pulmonary arterial pressure and pulmonary vascular resistance. During infusion there was also a significant rise in plasma H, epinephrine, and norepinephrine. All hemodynamic changes started 1-2 min after the beginning of H infusion and reverted to normal within 5 min from the end of the infusion. Subjective complaints were mild and transient in all patients. One patient progressed from first- to third-degree atrioventricular block, with prompt recovery of 1:1 atrioventricular conduction at the end of infusion. Thus, exogenous H administration in man at the rate of 0.4 microgram/kg/min produces significant and transient hemodynamic changes, mainly represented by systemic hypotension, tachycardia, and increased LV performance. These latter can be attributed to the associated increase in sympathoadrenergic activity, although a direct cardiac effect of H cannot be excluded.
To investigate the impairment of beta-adrenoceptor responsiveness in human hypertension, we evaluated the effect of an oral salt load (400 mEq/day of NaCl for 7 days) on plasma catecholamine concentrations and beta-adrenoceptor-mediated effects in 11 young patients with mild essential hypertension. Responses of heart rate and plasma cAMP to isoproterenol administration were used as indices of beta-adrenoceptor responsiveness. Salt loading induced a significant reduction in the dose of isoproterenol required to raise the heart rate by 25 bpm (CD25) (from 7.6 +/- 1.5 to 5.3 +/- 0.9 micrograms, p less than 0.05) and an increase in the slopes of the regression lines for heart rate changes and isoproterenol doses (delta HR/IS) (from 3.3 +/- 0.6 to 4.7 +/- 0.7, p less than 0.05) and for plasma cyclic AMP (cAMP) level changes and isoproterenol doses (delta cAMP/IS) (from 0.3 +/- 0.06 to 1.4 +/- 0.3, p less than 0.05). After salt loading there was a significant reduction in plasma catecholamine concentrations with a significant relationship between changes in upright plasma epinephrine levels and changes in CD25 (r = 0.904, p less than 0.01) and in the slopes for delta HR/IS (r = 0.983, p less than 0.001) and delta cAMP/IS (r = 0.922, p less than 0.001). These results support the hypothesis that the impairment of beta-adrenoceptor sensitivity observed in human hypertension is associated with a beta-adrenoceptor overstimulation due to chronically elevated adrenergic tone.
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