Noradrenaline levels in cerebrospinal fluid of drug-free and pimozide-treated schizophrenic patients.
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Biomedical subjects
Publications and source records attributed to M Volpe.
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1. The effects of intravenous administration of neostigmine and propranolol, individually or in combination, on baroreflex responsiveness have been evaluated in 18 borderline hypertensive subjects and in 14 age-matched control subjects. 2. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure, and heart rate and blood pressure changes induced by increasing neck-tissue pressure by means of a neck-chamber. 3. In borderline hypertensive subjects a reduced baroreflex responsiveness was demonstrated with both stimuli as compared with normal subjects. Neostigmine administration improved consistently both reflex responses. Similarly, after propranolol treatment, borderline hypertensive subjects showed a significant enhancement of the baroreflex sensitivity. Finally, the combined administration of neostigmine and propranolol restored the baroreflex responses. In fact, both the mean slopes of the regression lines between blood pressure and R-R interval after phenylephrine and the increase in mean arterial pressure and heart rate induced by the reduction in carotid transmural pressure in borderline hypertensive subjects were similar to those observed in normals. 4. These findings indicate that in borderline hypertensive subjects the impairment of baroreflex responsiveness is mainly due to abnormalities of autonomic regulation.
The effect of oral salt loading (400 mmol per day of NaCl for 7 days) on cardiac and pancreatic beta-receptor responsiveness has been evaluated in 12 patients with established essential hypertension and in seven age-matched control subjects. Cardiac beta-receptor responsiveness was evaluated by assessing the dose of isoprenaline which increased a stable heart rate by 25% (chronotropic dose 25%, CD 25%). Pancreatic beta-receptor responsiveness was measured by the incremental areas of insulin secretion induced by iv infusion of increasing amounts of isoprenaline. Before salt load, CD 25% was significantly higher in hypertensives compared with controls (7.84 +/- 1.34 micrograms vs 3.9 +/- 0.48 micrograms, P less than 0.05) while there was no difference in the isoprenaline-induced insulin secretion between the two groups of subjects. After salt loading, CD 25% was significantly reduced in hypertensive patients but was not modified in normal subjects. Therefore, the difference in CD 25% was no longer detectable between the two groups (5.5 +/- 1.42 micrograms vs 3.2 +/- 0.48 micrograms in normal subjects and in hypertensives, respectively, NS). Furthermore, salt loading failed to induce any change in isoprenaline-induced insulin secretion in either groups. These results support the existence of a relationship between sodium intake and adrenergic beta-receptor responsiveness in human hypertension.
Renal function in the basal state and after sodium load has been investigated in 21 borderline, hypertensive, first-degree relatives of established hypertensives and in 21 age- and sex-matched, normal subjects with no family history of hypertension. During intravenous infusion of inulin and p-aminohippurate in saline, both groups showed a decrease in plasma aldosterone levels (p less than 0.05) but renal plasma flow (595 +/- 48 vs. 750 +/- 59 ml/min, p less than 0.05), diuresis (1.4 +/- 0.2 vs. 2.2 +/- 0.5 ml/min, p less than 0.05), natriuresis (0.21 +/- 0.02 vs. 0.3 +/- 0.02 mEq/min, p less than 0.05) and sodium clearance (1.05 +/- 0.1 vs. 2.4 +/- 0.4 ml/min, p less than 0.05) in borderline hypertensives were higher than in the control group. After the salt load (NaCl, 1.35% i.v., 5 ml/min for 2 h) there was an increase in blood pressure and a decrease in plasma aldosterone and potassium levels in both groups. However, borderline hypertensives showed higher diuresis, natriuresis, sodium clearance and also kaliuresis compared to normotensives. These results suggest that borderline hypertensives already present the changes in renal function which are characteristics of established hypertensives.
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1. The reflex control of arginine-vasopressin release was studied in 12 essential established hypertensive patients and in 12 age-matched normal subjects by comparing the effects of head-up tilt and a variable-pressure neck-chamber. 2. After 45 min 85 degrees head-up tilt, normal subjects showed an increase in plasma arginine-vasopressin and in plasma renin activity, while plasma volume decreased. In hypertensive patients, plasma arginine-vasopressin showed changes after tilt opposite to those of controls, while the changes in plasma renin activity and plasma volume were similar to those observed in the normal group. In both groups the changes in systolic and diastolic blood pressure were not statistically significant. A reduction in carotid sinus transmural pressure obtained by increasing neck-tissue pressure (+50 mmHg) by means of a neck-chamber, evoked different responses in mean blood pressure in the two groups, but failed to induce any significant change in plasma arginine-vasopressin concentration both in the normal and in the hypertensive subjects. 3. These results seem to suggest that carotid sinus baroreceptors, though active in blood pressure control, do not play a direct role in arginine-vasopressin release and, therefore, the opposite response of arginine-vasopressin observed after tilt in the two groups of subjects should be ascribed to more complex mechanisms.
The baroreflex response to changes in transmural pressure throughout the arterial tree or limited to the carotid sinus was evaluated in ten borderline hypertensives and compared with that observed in ten normal subjects and in ten established hypertensives. Baroreceptor sensitivity was tested by evaluating both heart rate response to phenylephrine-induced increase in arterial pressure and heart rate and blood pressure changes induced by increased neck tissue pressure by means of a neck chamber. The heart rate response to phenylephrine (evaluated by the regression of the R-R interval versus the systolic blood pressure) was depressed both in borderline and established hypertensives as compared with controls. Similarly, the heart rate and the pressor response to increased neck tissue pressure were depressed in both groups of hypertensives. In borderline, but not in established hypertensives, neostigmine administration improved consistently the pressor baroreflex response to increased neck tissue pressure and the heart rate reflex response to both the employed stimuli. These findings indicate that a reduced parasympathetic activity is one of the components involved in the altered baroreflex sensitivity in borderline hypertensives.
The hemodynamic changes induced by coronary occlusion were investigated in anesthetized dogs. Coronary occlusion elicited an immediate but transient increase in the systemic blood pressure and in the vascular resistance of the hind limb perfused at constant flow. Thereafter, systemic hypotension and vasodilatation in the perfused region were observed. Vagotomy abolished the initial increase of the systemic and perfusion pressure and reduced significantly the late vasodilator response both systemically and in the perfused hind limb. After the subsequent administration of hexamethonium the vasodilatation in the hind limb was no longer manifest but the fall in blood pressure was unmodified. These results seem to suggest that multiple mechanisms are involved in the hemodynamic response to coronary occlusion.
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Systolic time intervals (STI) are regarded as good indices of cardiac performance in many heart diseases. It must be considered, however, that they are temporally related to the cardiac contraction cycle and, therefore, may be modified by heart rate changes. Thus, it is necessary to define the possible relationship between STI and heart rate changes. In this study, changes in heart rate were induced by atrial and ventricular pacing. Tachycardia caused a proportional decrease of left ventricular ejection time (LVET) (y=275.142-1.0025 x, r=0.76, p less than 0.001 for atrial pacing and y=298.28-0.691 x, r=-0.75, p less than 0.001 for ventricular pacing, respectively), but did not modify the pre-ejection period (PEP) and the isometric contraction time (ICT) and the electromechanical interval (QS1). These results demonstrate that while LVET must be corrected for the changes in heart rate, no correction of PEP and ICT is necessary.
In this study multivariate analysis was adopted to establish how simultaneous changes in heart rate (HR), blood pressure (BP) and work load (W) can affect systolic time intervals (STI). Thus, 13 normal volunteers underwent two consecutive exercise stress tests in the supine and upright position on a bicycle ergometer. By multivariate analysis it was shown that, while in the supine position left ventricular ejection time (LVET) is influenced by HR and W (LVET) = 330.6 - 0.76 HR - 0.41 W, F = 224, P is less than 0.001), in the upright position LVET changes are due only to HR variations (LVET = 309 - 0.88 HR, P is less than 0.001). Pre-ejection period (PEP) in both positions is related to HR and W, but this latter has a non-linear influence (supine: PEP = 110.9 - 0.15 HR -0.34 W + 0.0012 W(2), F = 56.4, P is less than 0.001; upright: PEP = 119 - 0.16 HR - 0.5 W + 0.0025 W(2), F = 86.7, P is less than 0.001). Finally, PEP/LVET ratio is correlated both in the supine and upright position with maximal BP, HR and W; however, the influence of HR and BP is different in the two positions (supine: PEP/LVET = 0.259 + 0.00047 BP + 0.00068 HR - 0.00167 W + 0.000013 W(2), F = 5.68, P is less than 0.01; upright: PEP/LVET = 0.201 + 0.0011 HR - 0.00371 W + 0.00016 W(2), F = 4.79, P is less than 0.01).
The hypotensive action of guanfacine and alpha-methyldopa has been compared in 30 patients wth moderate essential hypertension. After 2 weeks of placebo treatment, the patients were randomly allocated to a 12 week treatment with either of the two drugs. The treatment was started with guanfacine, 1 mg twice daily p.o., or alpha-methyldopa, 250 mg three time a day p.o. This dose of guanfacine was able to induce a satisfactory control of blood pressure in all patients while the dose of alpha-methyldopa was gradually increased to a predetermined maximum daily dose (2 g) in those patients with unsatisfactory blood pressure control, i.e., systolic blood pressure above 160 mmHg and diastolic above 95 mmHg. Then the two treatments were dicontinued for one week. Both drugs induced a significant reduction of systolic and diastolic blood pressure. However, guanfacine induced a more marked decrease in systolic blood pressure after the 14th day of treatment while the reduction of diastolic blood pressure was significantly higher only at the end of the final wash-out period, thus indicating a longer lasting effect of guanfacine as compared to alpha-methyldopa. Two patients treated with guanfacine developed dryness of the mouth and three of those in the alphamethyldopa group complained of excessive sedation.