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Biomedical subjects

M Fruscio

Publications and source records attributed to M Fruscio.

10 recordsLinked to original sources
PubMed1989

Cardiovascular and renal effects of single administration of three different doses of isradipine in hypertensive patients. Dose-response curves of the different effects.

The antihypertensive, humoral, and renal effects of acute single oral administration of placebo and isradipine, a new dihydropyridine calcium antagonist, at doses of 2.5 mg, 5.0 mg, and 7.5 mg once daily were investigated in 11 patients with mild-to-moderate uncomplicated essential hypertension. The patients maintained a constant daily intake of 100 mmol of sodium and 40 mmol of potassium. Placebo and isradipine were randomly administered to each patient, according to a Latin-square design, at intervals of at least 48 hours. The antihypertensive effect was dose-dependent and peaked at two hours after oral administration; changes at the lowest dose were already statistically significant (p less than 0.01). Increases in heart rate were mild and similar with all isradipine doses. Glomerular filtration rate and renal plasma flow showed a trend towards a dose-dependent rise; plasma renin activity was statistically increased (p less than 0.05) following the highest isradipine dose, whereas plasma aldosterone was unmodified. Isradipine resulted in a statistically significant rise (p less than 0.05) in sodium excretion and urine volume, which was similar with all active doses. In conclusion, the antihypertensive efficacy of isradipine is dose-dependent, whereas the natriuretic and diuretic effects are already at maximum following 2.5 mg per day, the lowest dose in this study.

Antihypertensive Agents↗
PubMed1989

Time-course of the changes in blood pressure and in plasma renin activity during the first week after dilation of renal artery stenosis.

We measured arterial pressure and plasma renin activity throughout the first week after a technically successful percutaneous transluminal renal angioplasty (PTRA) in 12 patients with hypertension and unilateral renal artery stenosis. Mean arterial pressure fell from 126 +/- 4 to 105 +/- 3 mmHg within 1-2 days of PTRA and stabilized thereafter; in addition, plasma renin activity decreased sharply during the first 2 days after the angioplasty (from 5.2 +/- 2.3 to 1.3 +/- 0.3 ng/ml per h) but continued to decline, reaching 0.8 +/- 0.2 ng/ml per h at the end of the study. When the antihypertensive effect of PTRA was examined in relation to baseline values of plasma renin activity, the patients with low, intermediate and high plasma renin activity showed percentage decreases in mean arterial pressure of, respectively, 6%, 16% and 19% by the sixth day of observation after the angioplasty. No overall correlation was found between the changes in arterial pressure and those in plasma renin activity induced by PTRA. These data suggest that the beneficial effect of PTRA on blood pressure can be estimated within a few days and that the reduction in the activity of the renin system is the principal but not the sole mechanism responsible for it.

Adult↗
PubMed1989

Nicorandil, a new vasodilator drug, in patients with essential hypertension.

In 12 mild to moderate hypertensive patients we investigated the acute antihypertensive efficacy of three different doses of nicorandil, a new vasodilating agent which probably acts by increasing the potassium efflux from smooth muscle cells and causing a cellular hyperpolarization. After a 3-day placebo period the patients were given, according to a double-blind Latin-square randomized design, 10, 20 and 30 mg nicorandil as a single acute dose every other day. Blood pressure and the heart rate were measured in both supine and upright positions at various times for 24 h after the dosing; fractional urine collections were obtained at the end of the placebo period and after each active dose. All doses of nicorandil similarly and significantly (P less than 0.01) reduced supine blood pressure, with a peak after 4-6 h (10 mg: -21/-8 mmHg; 20 mg: -20/-9 mmHg; 30 mg: -29/-17 mmHg), and the effect was still present, though reduced, after 24 h; no change in the heart rate was observed. The results from the upright position were similar. There were no significant changes in urine volume and electrolyte excretion during the nicorandil administration. The three different doses of nicorandil caused similar acute blood pressure reductions without change in the heart rate, nor in the urine volume and urinary sodium.

Adult↗
PubMed1988

Nifedipine does not blunt the aldosterone and cardiovascular response to angiotensin II and potassium infusion in hypertensive patients.

The antihypertensive response of calcium antagonists of the dihydropyridine series, although accompanied by a significant increase in plasma renin activity (PRA), is generally not associated with a comparably significant rise in plasma aldosterone (PA). This has been suggested to be due to the adrenal glomerular cell responsiveness being dependent on calcium entry. To investigate this hypothesis, angiotensin II (AII; 0.15, 0.375, and 0.750 micrograms/min, each step for 20 min) and KCl (30 mmol/50 min) were infused on separate days in 11 hypertensive patients kept at a constant daily intake of 100 mmol sodium and 40 mmol potassium, before and after 1 week of nifedipine treatment (20 mg b.i.d.). Supine blood pressure (BP) was significantly (p less than 0.01-p less than 0.001) reduced after nifedipine treatment; supine PRA increased significantly (p less than 0.01), while PA did not change significantly. No change in plasma potassium level was seen during nifedipine treatment. The dose-dependent mean BP rises induced by AII were slightly blunted during nifedipine treatment, whereas the PRA decreases and the PA rises after the peak infusion were not significantly different before and during nifedipine administration. Potassium infusion had no significant effect on BP, and caused a significant and similar rise in PA before and during nifedipine administration, while PRA decrease was more pronounced after nifedipine treatment. As previously shown in normotensive subjects, and also in hypertensive patients, aldosterone responses to two major stimulants, such as AII and potassium, do not appear to be blunted by treatment with a calcium antagonist.

Adult↗
PubMed1985

Antihypertensive and water and sodium balance effects of felodipine, a new vasodilating calcium antagonist, in hypertensive patients.

Felodipine, a new dihydropyridine derivative with a selective action on vascular smooth muscle, was investigated in 2 short term studies in hypertensive patients. In the first study, oral administration of felodipine 12.5 mg three times daily in a preliminary tablet formulation for 3 days significantly reduced supine and upright blood pressure with only a slight increase in heart rate and no clinically relevant signs of sodium and water retention. By increasing each dose to 25 and 50 mg three times daily, there was a further, but quite moderate, decrease in blood pressure; however, this was accompanied by an increase in heart rate and a tendency towards a reduction of creatinine clearance and urinary sodium output. In the second study, a new oral formulation containing 10 mg felodipine, administered twice daily for 7 days, was effective in lowering blood pressure without a clinically relevant tachycardia. Following the first dose of felodipine, urinary sodium excretion was slightly increased while potassium excretion showed only minor changes. The new calcium antagonist, felodipine, lowers blood pressure without the clinically relevant adverse reactions commonly related to other direct vasodilator antihypertensive drugs.

Adult↗
PubMed1985

Renal and antihypertensive effects of felodipine in hypertensive patients.

The effects of small doses of felodipine (10 mg twice daily) on blood pressure, renal function and sodium and water balance were studied in 11 patients with arterial hypertension. Felodipine significantly reduced systolic and diastolic blood pressure: most of the antihypertensive effect was already evident on day 1 of administration (-18/-11 mmHg) and only slightly increased during the subsequent week. Heart rate rose moderately only during day 1 of felodipine administration (+7 beats/min). Sodium excretion was increased during days 1 and 2, and no signs of water and electrolyte retention was observed in the week during which the balance study could be performed (Na, -135 +/- 65 mmol/7 days). At relatively low doses felodipine appears to be an effective antihypertensive agent, initially exerting some diuretic and natriuretic action and subsequently being devoid of a water- and sodium-retaining action.

Adult↗
PubMed1985

Does beta 1-selective agonistic activity interfere with the antihypertensive efficacy of beta 1-selective blocking agents?

In order to investigate whether addition of beta 1-selective agonism can interfere with the antihypertensive efficacy of beta 1-selective adrenoceptor blockers, two separate studies were carried out to evaluate the effects on blood pressure and heart rate of three beta 1-selective blockers with or without varying degree of beta 1-selective agonism. In hypertensive patients at rest, the greatest blood pressure reduction and bradycardia were found with atenolol, a beta 1-selective blocker without any agonistic activity; a consistently smaller effect on blood pressure and heart rate was observed with Visacor (ICI 141 292), a beta 1-selective blocker with moderate beta 1-selective agonism, whereas no clinically relevant decrease in blood pressure occurred with Corwin (ICI 118 587), the beta 1-selective blocker with high beta 1-selective agonism. In contrast, during exercise-induced sympathetic activation, all three compounds reduced systolic blood pressure and heart rate to a similar degree.

Adrenergic beta-Agonists↗
PubMedDate not supplied

Effects of single and repeated doses of the calcium antagonist felodipine on blood pressure, renal function, electrolytes and water balance, and renin-angiotensin-aldosterone system in hypertensive patients.

Doses of 10 mg b.i.d. of the new dihydropyridine calcium antagonist, felodipine, were tested for seven consecutive days in 11 hospitalized hypertensive patients. A significant reduction of both systolic and diastolic blood pressures, with patients in both the supine and upright positions, occurred immediately after the first dose and was maintained (daily average 15%) throughout the following days. An increase in heart rate was observed after the first dose (15 and 23 beats/min, in supine and upright postures), and subsequently declined to average values of 8 and 14 beats/min on the seventh day. There was a marked natriuretic response during the first and second day, during which an average negative sodium balance of 95 mmol developed; on the following days sodium output was not significantly different from control, but a negative balance averaging 135 mmol was still present on the seventh day of felodipine administration. A moderate negative potassium balance also progressively developed and reached -48 mmol on the seventh day. Glomerular filtration rate was unchanged, but renal plasma flow increased significantly during administration of felodipine. Plasma renin activity and plasma aldosterone were also increased very moderately by felodipine. Compared with previous observations by our group with higher doses of felodipine (12.5, 25, and 50 mg t.i.d.), 10 mg b.i.d. of this new calcium antagonist appear to exert a marked and prolonged blood pressure reduction, accompanied by a definite natriuretic instead of an antinatriuretic effect.

Adult↗
PubMedDate not supplied

Felodipine, a new vasodilating drug: blood pressure, cardiac, renal, and humoral effects in hypertensive patients.

We studied the antihypertensive action of felodipine, a new dihydropyridine vasodilator interfering with intracellular calcium mechanisms, in 11 patients with essential hypertension whose supine blood pressure averaged 181/109 mm Hg after 5 days of placebo administration. Felodipine, 12.5 mg t.i.d., for 3 days, caused a marked reduction (-39/-19 mm Hg) of supine systolic and diastolic pressures. Doses of 25 and 50 mg t.i.d., for three consecutive days, caused only a slight further reduction of blood pressure. At the highest dose tested all patients had their supine blood pressure brought down to values below 150 mm Hg systolic and 90 mm Hg diastolic at all six daily measurements. The antihypertensive effect was of the same magnitude when the patients lay supine or stood upright. Lowering of blood pressure was accompanied by tachycardia, which was quite moderate after the 12.5 mg t.i.d. dose, but more conspicuous with the two higher doses. There was some increase in plasma renin activity and in plasma aldosterone. A significant decrease in renal sodium and water excretion occurred only during administration of the highest dose of 50 mg t.i.d., when reduction in blood pressure was pronounced and there were reflex increases in plasma renin activity and plasma aldosterone.

Aldosterone↗