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G Sperti

Publications and source records attributed to G Sperti.

33 records · Page 2Linked to original sources

Calcium influx modulates DNA synthesis and proliferation in A7r5 vascular smooth muscle cells.

In A7r5 vascular smooth muscle cultures basal Ca2+ influx was higher in growing versus quiescent cells (P less than 0.05), due primarily to a five-fold increase in dihydropyridine-inhibitable Ca2+ influx (P less than 0.005). Verapamil decreased [3H]thymidine incorporation in a concentration dependent fashion with a significant 6 +/- 2% inhibition at 0.1 microM and a maximal inhibition of 67 +/- 2% at 100 microM. Similarly, nitrendipine inhibited fetal calf serum-stimulated [3H]thymidine incorporation with a threshold concentration of 1 nM and a maximal inhibition of 79 +/- 12% at 10 microM. In quiescent cells, verapamil (10 microM) inhibited the increases in [3H]thymidine incorporation stimulated by fetal calf serum, serotonin, vasopressin or 12-0-tetradecanoyl phorbol-13-acetate by 37-43% (P less than 0.001 vs. control for all). Finally, verapamil (100 microM) and nitrendipine (10 microM) inhibited proliferation by 39 +/- 10 and 20 +/- 6%, respectively (P less than 0.01 and 0.02 vs. control, respectively). Thus in A7r5 cells, proliferation is associated with increased Ca2+ influx via dihydropyridine-sensitive Ca2+ channels and organic Ca2+ channel antagonists inhibit DNA synthesis and cell proliferation.

Animals↗

Phorbol ester increases the dihydropyridine-sensitive calcium conductance in a vascular smooth muscle cell line.

In vascular smooth muscle, phorbol esters cause a slowly developing contraction and an associated transmembrane calcium flux, both of which are inhibited by dihydropyridine calcium channel antagonists. In the A7r5 cultured vascular cell line, we used the whole-cell voltage-clamp technique to identify voltage-dependent calcium conductances and investigate the effect of phorbol esters on that conductance having characteristic dihydropyridine sensitivity (slowly inactivating, high-threshold, "L-type"). With barium as the charge carrier, large-amplitude (100-800 pA) inward currents of two types were characterized by their kinetics and voltage dependence. With holding potential--80 mV, a rapidly inactivating, low-threshold current ("T-type") was activated by depolarizations above-40 mV and was maximal at -10 mV. With holding potential -30 mV, this component was inactivated, and a second slowly inactivating, high-threshold current was activated above -10 mV and was maximal at +10 to +20 mV. These currents are similar to the T-type and L-type currents previously described in vascular smooth muscle cells. When added to the bath, the active phorbol ester, 12-O-tetradecanoyl phorbol-13-acetate (100 nM) increased the slowly inactivating (L-type) current by 32 +/- 20% (n = 8, +/- SD). Phorbol-12,13-dibutyrate (100 nM) caused a similar effect, but the inactive phorbol, 4-alpha-phorbol (100 nM), did not. We conclude that at least two distinct calcium conductances are expressed in A7r5 vascular smooth muscle cells, and that the dihydropyridine-sensitive calcium conductance is acutely modulated by phorbol esters, presumably acting through stimulation of protein kinase C. Such modulation may play a role in increasing transmembrane calcium influx mediated by agonist-receptor interactions that lead to activation of protein kinase C and may help to sustain or amplify calcium-dependent cell responses.

Animals↗

Phorbol ester-stimulated bidirectional transmembrane calcium flux in A7r5 vascular smooth muscle cells.

In A7r5 vascular smooth muscle cells, the phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) caused a marked increase in the rate of unidirectional Ca2+ influx and a 63 +/- 9% increase in net 30-min 45Ca2+ uptake. Maximal TPA-stimulated 45Ca2+ uptake occurred at concentrations less than or equal to 3 nM and was equivalent to the maximal uptake stimulated by 55 mM KCl or 1 microM Bay k 8644. TPA-stimulated Ca2+ uptake was not additive to KCl- or Bay k 8644-stimulated uptake, and was inhibited by verapamil (100 microM), nitrendipine (1 microM), or high concentrations of Bay k 8644 (greater than or equal to 10 microM). The biologically inactive phorbol ester 12-O-tetradecanoyl phorbol-13-acetate methyl ether (10 nM) had no effect on 45Ca2+ uptake. TPA caused a 43 +/- 12% increase in Ca2+ efflux in 30 min, and exposure to TPA (10 nM) for 5 and 30 min caused no significant change in net cellular Ca2+ content as determined by radioisotopic equilibration or atomic absorption spectroscopy. TPA caused no apparent change in intracellular free Ca2+ concentration as determined with quin 2. Thus, in A7r5 cells, TPA causes a marked increase in Ca2+ influx through channels with the pharmacological characteristics of dihydropyridine-sensitive, voltage-dependent channels. This TPA-stimulated Ca2+ uptake is associated with increased Ca2+ efflux and no significant change in net cellular Ca2+ content or intracellular free Ca2+ concentration.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Evaluation of blood pressure control after bilateral glomectomy: effects of propranolol treatment.

The effects of bilateral glomectomy on arterial blood pressure and heart rate and the response to the pressor tests were studied in a women of 37. Arterial pressure and ECG were recorded by the continuous unrestricted Oxford method. Hypotension, increased blood pressure variability and tachycardia rapidly developed 2 days after surgery, indicating sympathetic hyperactivity and/or deactivation of vagal tone. Wide blood pressure fluctuations were present on standing and abnormal blood pressure responses to head up tilting and to the Valsalva maneuver were observed reflecting a less prompt and precise control of blood pressure. Treatment with propranolol reduced tachycardia and blood pressure variability. After 5 and 17 months of this therapy propranolol was withheld for 36 h. Tachycardia was still present and blood pressure fluctuations were recorded on assuming the upright posture. However, the heart rate and pressure response to the Valsalva maneuver were normal after 17 months, indicating an improvement of the reflex control of blood pressure.

Adult↗

Prevalence and possible mechanisms of ventricular arrhythmias in athletes.

To investigate the prevalence and nature of ventricular arrhythmias in athletes, 40 well trained healthy endurance athletes (20 cyclists and 20 runners) and 40 healthy sedentary subjects as controls were studied. Twenty four-hour continuous ECG monitoring showed a higher, even though not significant prevalence of ventricular ectopy in athletes (70% vs 55%). Complex forms of ventricular ectopy were also more prevalent in the athletes than in the controls (25% vs 5%; p less than 0.05). A prolongation of both measured QT interval and QT corrected for heart rate was observed at the ECG. Echocardiograms showed higher dimensional indices in the athletes, while functional indices were similar in athletes and controls. No correlation was found between any ECG or echocardiographic finding and the grade of ventricular arrhythmia. The comparison between the cyclists and the runners did not show any significant difference in the prevalence of ventricular arrhythmias or in the QT interval duration.

Adult↗

Evaluation of hypertension and related target organ damage by average day-time blood pressure.

Aim of the present study was to verify whether average blood pressure continuously recorded throughout the day correlates with the degree of target organ damage more closely than casual pressure in hypertensive patients. The study was conducted in 102 subjects with borderline, moderate and severe hypertension. Our results confirm a closer relationship between cardiovascular complications and recorder blood pressure than casual pressure possibly because the latter less perfectly reflects the patients usual pressures which are generally lower. However our results further demonstrate that blood pressure variability also contributes to the degree of target organ damage since for equal average day-time pressures a greater severity of cardiovascular complications was observed in patients with the highest blood pressure variability and the highest peaks of pressure. These findings should be carefully considered when evaluating the effect of antihypertensive drugs.

Adolescent↗

Reliability of indirect blood pressure monitoring for the evaluation of hypertension.

To assess the reliability of the Del Mar Avionics indirect blood pressure (BP) monitoring system 15 hypertensive patients were concomitantly studied with the intraarterial Oxford system. During daytime a statistically significant correlation was found between the BP values obtained with the two systems. On the contrary during the night this correlation in most cases was not significant. However the histograms of the between-method differences were similar during the day and the night, showing that the Del Mar Avionics Pressurometer (P) performs equally well throughout the 24 hours. It is concluded that the P is reliable for continuous indirect BP monitoring and suitable for the evaluation of the efficacy of antihypertensive treatments.

Blood Pressure↗

Computer analysis of continuous direct blood pressure recording.

Blood pressure signals recorded continuously in ambulatory patients using the Oxford system were analyzed by an IBM 370 computer in order to obtain beat by beat systolic and diastolic blood pressure along 24 hour blood pressure recordings. The analogical-digital conversion of the signal and the analysis of the sphygmogram are presented and discussed. Synthesis of the several thousands data obtained in 24 hour recordings and plotting of the data for clinical purposes and pharmacological studies are also reported.

Blood Pressure↗

[Treatment of refractory hypertension with combined minoxidil and captopril in low doses].

Twelve patients with severe hypertension of different causes, resistant to conventional antihypertensive agents and also to maximum doses of either minoxidil or captopril added to other combinations, were effectively controlled with the association of small doses of minoxidil and captopril plus a diuretic and a beta-blocker. The untoward effects which were previously present in all the patients with maximum doses of minoxidil and in one of the patients treated with captopril disappeared or greatly diminished shortly after this association was started. The different mechanisms of action and opposite side effects of minoxidil and captopril provide the rationale for a combined treatment with the two drugs.

Adrenergic beta-Antagonists↗

[Drug-induced orthostatic hypotension can be useful in antihypertensive therapy].

The evaluation of the efficacy of antihypertensive therapy may be misleading if it is based on office blood pressures which are usually higher than ambulatory or home pressures. An erroneous evaluation may also derive from the presence of orthostatic hypotension induced by antihypertensive therapy. In seven patients with moderate to severe hypertension who were treated with different antihypertensive agents and who presented drug-induced orthostatic hypotension we studied 24 hour blood pressures by means of the Oxford system. The mean of the blood pressures recorded with the patients up and about were lower than with the patients in the supine position. Consequently the physiological fall in blood pressure which is present in untreated patients during sleep was not observed. The following conclusions may be drawn: a) drug-induced orthostatic hypotension may be useful in antihypertensive therapy; b) drugs which are capable of reducing blood pressure particularly in the supine position should be preferred during the night; c) for the evaluation of antihypertensive therapy it is necessary to take into account both supine and standing blood pressure.

Adult↗

[Hypotensive effect and changes of arterial pressure variability induced by treatment with labetalol in patients with slight and moderate arterial hypertension].

To evaluate the hypotensive efficacy of labetalol (600 mg/day) six mild to moderate hypertensive patients were studied by the indirect continuous blood pressure monitoring with the Del Mar Avionics Pressurometer 111 degrees. This technique gives a much larger number of blood pressure values in a greater variety of conditions than the conventional Riva-Rocci sphygmomanometer. After one month of continuous therapy there was a substantial reduction in systolic and diastolic pressure. The increased index of Kurtosis revealed a decreased blood pressure variability. The circadian changes of blood pressure were not significantly affected, but the morning peak was smoothed by labetalol.

Blood Pressure↗

Intravenous labetalol in severe hypertension.

1 Labetalol was administered by intravenous infusion or by the combination of intravenous bolus injection plus infusion to 15 patients with severe essential hypertension and to one with phaeochromocytoma. 2 With the infusion alone the reduction of arterial pressure was slow to develop and limited in degree, but with the combination of the bolus injection plus the infusion the reduction in pressure was more prompt, more pronounced and longer lasting. Apart from an uncomplicated syncopal attack in one patient, no serious side--effects were encountered. 3 Subsequent treatment with oral labetalol usually required the addition of a diuretic to control the blood pressure probably due to sodium and fluid retention during treatment with labetalol alone.

Administration, Oral↗