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Biomedical subjects

J F Prost

Publications and source records attributed to J F Prost.

At least 37 records · Page 2Linked to original sources
PubMed1992

Role of angiotensin subtype 2 receptor in neointima formation after vascular injury.

The role of angiotensin receptor subtypes 1 and 2 was assessed on neointima formation after injury in rat carotid artery. The effects of angiotensin converting enzyme inhibition by perindopril (3 mg.kg-1 x day-1 p.o.) and selective blockade of angiotensin subtype 1 receptors by DuP 753 (5 and 30 mg.kg-1 x day-1 p.o.) were compared on proliferative response to balloon injury. In rats treated 6 days before and for 14 days after injury, perindopril significantly reduced (-76%, p < 0.01) myointimal hyperplasia. In contrast, DuP 753 at 5 mg.kg-1 x day-1 did not modify the hyperplastic response to balloon catheterization. Only at 30 mg.kg-1 x day-1 was DuP 753 able to reduce neointima formation (-47%, p < 0.05). This dose was equipotent to perindopril on the renin-angiotensin system as assessed by the pressor response to angiotensin II and angiotensin I. Therefore, blockade of subtype 1 receptors was a less effective means of suppression of myointimal growth than angiotensin converting enzyme inhibition, suggesting that another angiotensin receptor subtype or converting enzyme substrates are involved in this process. For the determination of whether angiotensin subtype 2 receptors were implicated, the specific subtype 2 receptor antagonist CGP 42112A (1 mg.kg-1 x day-1) was continuously infused perivascularly for 14 days in the vicinity of the injured carotid artery. CGP 42112A was as effective in preventing neointima formation as perindopril (-73%, p < 0.01, versus -76%, p < 0.01, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1991

Comparison of the effects of intravenous almitrine and positive end-expiratory pressure on pulmonary gas exchange in adult respiratory distress syndrome.

The effects of almitrine on pulmonary gas exchange and haemodynamics were compared to those of positive end-expiratory pressure (PEEP) in 10 patients with a severe adult respiratory distress syndrome (ARDS) who required continuous mechanical ventilation. Haemodynamic and gas exchange measurements were made before and after 30 min of PEEP at a level of 10 cmH2O, then 30 min later, before and at the end of the intravenous infusion of almitrine at a dose of 0.25 mg.kg-1 in 30 min. There was no significant difference between baseline gas exchange and haemodynamic parameters. PEEP and almitrine increased Pao (p = 0.001) from 10.9 to 12.6 kPa and from 10.6 to 12.6 kPa (1 kPa = 7.5 mmHg), respectively, and ratio of venous admixture to total blood flow (Qs/Qt) decreased (p less than 0.001) from 34 to 29% and from 33 to 29%, respectively, the effects of PEEP and almitrine being not significantly different. Neither PEEP nor almitrine caused a significant change in arterial carbon dioxide tension (PaCO2). The haemodynamic parameters did not change significantly with almitrine, whereas mean systemic arterial pressure decreased from 85.4 to 81.1 mmHg (p less than 0.05) with PEEP. These results are consistent with the hypothesis that both treatments improve ventilation/perfusion (VA/Q) distributions, by an increase in functional residual capacity in the case of PEEP and a redistribution of pulmonary perfusion in the case of almitrine.

Adult↗
PubMed1990

Beta blockers induce different intrarenal effects in humans: demonstration by selective infusion of tertatolol and propranolol.

The effects of tertatolol and propranolol on renal circulation were studied in patients with normal renal function to test the hypothesis that various beta blockers may have different vasomotor effects within the renal vascular bed. Left renal blood flow was measured by the continuous thermodilution method before (t0), and 5 (t1), 10 (t2), 20 (t3), and 30 (t4) minutes after a selective infusion of tertatolol (0.25 mg, N = 4) or propranolol (2.5 mg, N = 4) into the left renal artery. Heart rate, cardiac output, aortic and right atrial pressures, and systemic vascular resistances did not significantly vary after either drug throughout the study. Plasma renin activity and plasma aldosterone in arterial and renal venous blood started to decrease at t1 after each drug. After propranolol, renal blood flow, renal vascular resistance and the renal arteriovenous oxygen difference were unchanged. Conversely, after tertatolol at t3, renal blood flow was increased (from 426 +/- 18 mL/min/1.73 m2 to 509 +/- 56 mL/min/1.73 m2, P = .03), renal vascular resistance and renal arteriovenous oxygen difference were decreased (P less than .001), and the renal blood flow/cardiac output ratio was increased (P = .03). The filtration fraction did not vary after either drug, as attested by the unchanged polyfructosan extraction coefficient. This clinical study shows that selective infusion of a single low dose of tertatolol into the renal artery results in a delayed intrarenal vasodilator effect, while at the dose tested propranolol does not modify renal hemodynamics.

Adrenergic beta-Antagonists↗
PubMed1989

Effect of tertatolol on glomerular hemodynamics in the normal Munich-Wistar rat.

Administration of beta-blockers is frequently associated with decreases in both renal plasma flow and glomerular filtration rate (GFR). Tertatolol, a new non-selective beta-blocker, has demonstrated similar systemic effects to other conventional beta-blockers, but tertatolol produces increases in both renal plasma flow and glomerular filtration rate. To evaluate the renal hemodynamic mechanism responsible for the increase in GFR, micropuncture experiments were performed in normal Munich-Wistar rats. Intravenous injection of tertatolol produced a significant increase in GFR and urinary sodium excretion in spite of a decrease in systemic blood pressure. Single nephron glomerular filtration rate was significantly increased due to an increase in single nephron plasma flow related to parallel afferent and efferent arteriolar dilatation. No significant changes in glomerular hydrostatic pressure, transcapillary hydrostatic pressure gradient or the ultrafiltration coefficient were demonstrated with tertatolol. The capacity of tertatolol to increase glomerular filtration rate and to promote sodium excretion without modifying critical glomerular pressures makes this agent a highly attractive antihypertensive drug.

Adrenergic beta-Antagonists↗
PubMed1989

Selective infusion of tertatolol into the renal artery induces a local vasodilator effect in humans. Demonstration by the continuous thermodilution method.

The effects of tertatolol on renal circulation were studied in 8 patients with normal renal function. Left renal blood flow was measured by the continuous thermodilution method before (t0), and 5 (t1), 10 (t2) and 20 (t3) min after a selective infusion of 0.25 mg of tertatolol into the left renal artery. During the study, cardiac output, heart rate, aortic and right atrial pressures, systemic vascular resistances and the systemic arteriovenous oxygen difference were not significantly altered. Plasma renin activity and plasma aldosterone in arterial and renal venous blood started to decrease at t1. At t3, renal blood flow was increased (from 463 +/- 28 mL/min at t0, to 549 +/- 22 mL/min, P less than .001), renal vascular resistance was reduced (from 188 +/- 17 mm Hg/L/min at t0 to 156 +/- 15 mm Hg/L/min, P less than .01) and the arteriovenous oxygen difference was decreased (from 1.6 +/- 0.2 mL/100 mL at t0 to 1.1 +/- 0.1 100 mL, P less than .01). The renal/cardiac flow ratio increased from 10.0 +/- 2.2% to 11.7 +/- 2.1% (P less than .05) and the renal/systemic vascular resistance ratio decreased from 10.5 +/- 2.0 to 8.7 +/- 1.4 (P less than .01). These data show that selective infusion of a low dose of tertatolol into the renal artery results in an increase in renal blood flow which is delayed and occurs without concomitant changes in systemic hemodynamics. This suggests an intrarenal mechanism of action in humans supporting the previously observed renal vasodilation induced by tertatolol in isolated perfused animal kidneys.

Adult↗
PubMed1989

The Tertatolol International Multicenter Study (T.I.M.S.). Predicting factors of an efficient therapy.

The Tertatolol International Multicenter Study (T.I.M.S.) was aimed at assessing the efficacy and tolerability of 5 mg tertatolol (T) once daily over a one year period and at finding, among the clinical variables before treatment, parameters predicting a successful single beta-blocking therapy. The study was carried out in 230 patients (96 men, 134 women, mean age +/- standard error of the mean: (51.5 +/- 0.7 years) suffering from uncomplicated mild to moderate hypertension. After a one-month placebo run-in period (M0-M1) and a one-month double-blind placebo-controlled period (M1-M2), 213 patients entered and 166 completed the one-year open period (M2-M14). A diuretic (D) was added if blood pressure (BP) was inadequately controlled with the single therapy. After one year, 88.5% of patients were controlled (sitting diastolic BP less than or equal to 90 mm Hg): 56.3% on single therapy (T) and 32.2% on dual therapy (T + D), respectively. Statistical analysis performed on the controlled subjects showed that patients who were controlled with T alone had an initially lower standing diastolic BP and a higher standing heart rate, were younger and had a lower sitting systolic BP than those controlled with T + D. Using such discriminant parameters which are predictors, 83.5% patients (single therapy group) and 49% patients (dual therapy group) were classified in the therapeutic group to which they really belonged. This study confirms the antihypertensive efficacy of tertatolol, and highlights relevant parameters for a successful single beta-blocker therapy in clinical practice.

Adrenergic beta-Antagonists↗
PubMed1989

Tertatolol increases glomerular filtration and urinary sodium in anesthetized rats.

Tertatolol is a new beta-adrenergic blocking agent that possesses unique actions on kidney function. In the present study, the effect of increasing doses of tertatolol (0.025, 0.05, 0.1, 0.2 and 0.3 mg) was examined in different groups of anesthetized rats and the results compared with injection of the vehicle. Bolus i.v. injections of tertatolol resulted in a dose-related elevation of urine volume (UV), from 4.1 +/- 0.3 to 6.0 +/- 0.4, 10.2 +/- 1.3, 13.8 +/- 1.2, 18.8 +/- 1.9 and 16.4 +/- 1.8 microliters/min, respectively. Similarly, urine Na increased from 0.4 +/- 0.1 to 0.8 +/- 0.2, 1.2 +/- 0.2, 2.2 +/- 0.3, 3.4 +/- 0.7 and 2.9 +/- 0.6 mueq/min. These changes were associated with a progressive rise in glomerular filtration rate (GFR) from a mean control value of 1.15 +/- 0.10 to 1.28 +/- 0.09, 1.41 +/- 0.07, 1.50 +/- 0.10, 1.62 +/- 0.16 and 1.48 +/- 0.07 ml/min. No change in urinary phosphate excretion was observed. In a separate group of studies, the effect of tertatolol was compared with propranolol (1 mg): the maximal elevation on UV and urine Na was less than 25% of that obtained with tertatolol. Elevation of GFR was also 30% higher in animals receiving tertatolol. The effect of tertatolol on UV and urine Na resulted in part from the rise in GFR but also from tubular inhibition of Na transport, since fractional Na excretion increased from 0.24 +/- 0.09 to a maximal value of 1.76 +/- 0.10%. This tubular action presumably occurs beyond the proximal nephron, because no effect on urinary phosphate excretion was obtained during tertatolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1988

Preserved renal perfusion during beta blockade by tertatolol with and without cyclooxygenase inhibition in normal humans.

The systemic and renal hemodynamic effects of tertatolol, a new noncardioselective beta blocker without partial agonist activity, given alone or in combination with cyclooxygenase inhibition by acetylsalicylic acid (aspirin), were investigated in eight healthy volunteers. Tertatolol 5 mg, aspirin 1 g, tertatolol 5 mg together with aspirin 1 g and placebo were administered at 1-week intervals in a random order and in a double-blind fashion. Cardiac output was measured by Doppler echography and renal blood flow and glomerular filtration rate (GFR) by constant infusion techniques using (123I) iodohippurate and (51Cr) EDTA, respectively. Measurements were performed before and then successively 2 and 4 hours after oral intake of drugs or placebo. Tertatolol decreased cardiac output by 22% (P less than .05) and heart rate by 17% (P less than .05) without change in blood pressure, renal blood flow, and GFR. The same effects occurred when tertatolol was given together with aspirin. Either placebo or aspirin alone had no effect on systemic and renal hemodynamics. These results suggest that cardiac output is redistributed to the kidneys after tertatolol intake in normal humans. This favorable effect on renal hemodynamics is probably not mediated by a local release of vasodilating prostaglandins.

Adult↗
PubMed1988

Acute effects of tertatolol and nadolol on systemic and renal hemodynamics in patients with essential hypertension.

The acute systemic and renal hemodynamic effects of tertatolol, a new noncardioselective beta-blocker without partial agonist activity, were compared to those of an equipotent dose of nadolol in eight patients with essential hypertension. Tertatolol (5 mg) or nadolol (80 mg) were administered orally at an interval of 1 week in a random order as a double-blind, cross-over study. Cardiac output was measured by Doppler echography, and renal blood flow and glomerular filtration rate were measured by constant infusion techniques using 123I-iodohippurate and 51CR-EDTA, respectively. Measurements were performed before and then successively 2 and 4 hours after ingestion of the drugs. Both nadolol and tertatolol decreased blood pressure and cardiac output to a comparable extent. Renal blood flow remained unchanged, so that the renal fraction of cardiac output increased from 14.4 +/- 1.5% to 21.3 +/- 2% after nadolol and from 14.8 +/- 2.4% to 20.5 +/- 1.8% after tertatolol (mean +/- SE, P less than 0.01 before vs. after; nadolol vs. tertatolol was not significant). The glomerular filtration rate remained unchanged, from 68 +/- 9 to 64 +/- 6 mL/min.m2 after nadolol and from 71 +/- 8 to 67 +/- 7 mL/min.m2 after tertatolol (before vs. after and nadolol vs. tertatolol levels were not significant). These results show that both tertatolol and nadolol redistribute cardiac output to the kidneys in patients with essential hypertension.

Adult↗
PubMed1988

The beta adrenoceptor blocker tertatolol causes vasodilatation in the isolated perfused vasoconstricted rat kidney.

The activity of the beta adrenoceptor antagonist tertatolol on renal vasoconstrictions was investigated. Infusion of increasing concentrations of tertatolol (10(-8) to 10(-5) M) progressively inhibited the constrictor responses to bolus injections of norepinephrine and to electrical stimulation in isolated perfused kidneys of both normotensive and spontaneously hypertensive rats. Also, in kidneys of normotensive rats the vasoconstrictions caused by serotonin and barium chloride were inhibited by tertatolol. During sustained vasoconstrictions induced by infusion of norepinephrine (6 X 10(-7) M) increasing doses of tertatolol (2.5 X 10(-7) g to 2 X 10(-5) g) caused rapid, reversible dilatations in the rat kidneys. The inhibitory responses caused by tertatolol were not antagonized by propranolol, atropine, hexamethonium, SCH23390, metoclopramide, mepyramine, cimetidine, naloxone, cocaine or indomethacin. During constrictions caused by norepinephrine, methylene blue significantly inhibited the renal vasodilatations caused by tertatolol, acetylcholine, papaverine and nitroglycerin but not those caused by atrial natriuretic factor. Unlike the other vasodilators, tertatolol did not inhibit the constrictions induced by prostaglandin F2 alpha (5 X 10(-6) M) in the rat kidneys. In canine renal arteries with endothelium, tertatolol (10(-9) to 10(-5) M) did not cause relaxations during contractions induced by norepinephrine, electrical stimulation or prostaglandin F2 alpha. Our data illustrate that tertatolol has potent vasodilator properties in the isolated perfused vasoconstricted rat kidney. The dilator response to the beta blocker cannot be inhibited by a variety of classical receptor blockers but ultimately seems to depend on the formation of cyclic GMP.

Adrenergic beta-Antagonists↗
PubMed1987

Airway response to salbutamol and to ipratropium bromide after non-selective and cardioselective beta-blocker.

Eight healthy men were randomly assigned in a latin square order to receive single doses of placebo, tertatolol 5 mg, propranolol 80 mg and atenolol 100 mg at 7-day intervals. Resting heart rate and pulmonary function were measured 10 min before and over the 240 min following dosing, and then 15 min after inhalation of salbutamol 200 micrograms and ipratropium bromide 40 micrograms. The three beta-blockers caused similar reductions in resting heart rate throughout the study, whereas placebo had no effect. The three beta-blockers, like placebo, produced no significant change in pulmonary function during the 240 min after dosing. The bronchodilator response to salbutamol after atenolol and placebo was preserved, whereas it was reduced after administration of either of the non-selective beta-blockers, tertatolol and propranolol. An unequivocal response of the airways to ipratropium bromide was observed after tertatolol and propranolol, which was much greater than after atenolol. No response was observed after placebo. Thus, despite bronchial beta 2-blockade, by non-selective beta-blockers, bronchodilatation was definitely produced by ipratropium bromide, confirming the predominant role of the parasympathetic system in the autonomic innervation of normal human airways.

Adrenergic beta-Antagonists↗
PubMed1987

Prolonged beta blockade due to tertatolol: a comparative study with propranolol and atenolol.

Submaximal exercise heart rate was measured after oral administration of placebo, tertatolol 5 mg, propranolol 80 mg, and atenolol 100 mg to 12 subjects in a double-blind cross-over study. The peaks of beta-blocking activity, observed at 2 hr, were of similar extent for the 3 drugs. The duration of activity of tertatolol, a beta blocker with a short elimination half-life, extended up to 24 hr as did that of atenolol, but was longer than that of propranolol which reached only 18 hr. These results support once-daily administration of tertatolol in therapy.

Adult↗
PubMed1986

Mathematical modelling accounting for discrepancies between blood levels and pharmacodynamic effects of a drug. Application to the numerical optimization of tertatolol.

In this paper we propose a non-linear model for explaining the relation between doses, blood levels and pharmacodynamic effects. Several models are examined and a functional relation (without derivatives or integrals) is retained. From there the medical system is optimized by using optimal control methods. In practice, optimal doses and times are numerically determined for the drug tertatolol.

Adult↗
PubMed1986

Reduction of beta-adrenergic receptors by tertatolol: an additional mechanism for beta-adrenergic blockade.

Tertatolol is a potent new beta-blocker with no intrinsic sympathomimetic activity or beta 1/beta 2-receptor subtype selectivity. When given at therapeutic doses (5 mg/day) to human subjects it induced a reduction in the beta-adrenergic receptor number measured by 3H-CGP 12177 specific binding, without any change in the affinity on intact lymphocytes. This reduction was seen 7 hours (54%), 24 hours (35%), and 48 hours (30%) after a single drug dose. A similar receptor reduction was observed 7 hours (42%), 24 hours (37%), and 48 hours (15%) after 14 doses of the drug. In parallel, the pharmacologic efficacy of the drug was evident from the reduction in supine and upright heart rates and after submaximal exercise; heart rate was reduced to the same extent after single or repeated drug doses. The reduction of receptor number correlated well with the reduction in heart rate in the supine (P less than 0.001) and upright (P less than 0.01) positions and after exercise (P less than 0.02). In in vitro competitive binding experiments tertatolol was found to be a competitive inhibitor of beta-adrenergic receptors. However, on intact human lymphocytes preincubated with this drug, tertatolol reduced the density of beta-adrenergic receptors. We conclude that tertatolol, besides competitively inhibiting beta-adrenergic receptors, induced a marked and lasting decrease in the beta-adrenergic receptor number. This effect may be important for its beta-blocking effects.

Adrenergic beta-Antagonists↗
PubMed1986

Acute central and renal haemodynamic responses to tertatolol and propranolol in patients with arterial hypertension following head injury.

We compared the central and renal haemodynamic effects of tertatolol, a new non-cardioselective beta-adrenergic blocking drug without partial agonist activity, with those of an equipotent dosage of propranolol in two groups of 10 patients each with acute cerebral injury who had developed systemic hypertension. After tertatolol, 5 mg orally, mean arterial pressure was unchanged, heart rate decreased by 22% (P less than 0.01) and cardiac index by 24% (P less than 0.01), while renal blood flow remained unchanged (-5%, NS). After 160 mg propranolol orally, mean arterial pressure was unchanged, heart rate decreased by 12% (P less than 0.01), cardiac index by 16% (P less than 0.01) and renal blood flow by 17% (P less than 0.01). There was a moderate rise in norepinephrine levels after tertatolol only. Thus in this particular model of acute hypertension, tertatolol acted as a potent beta-blocking agent but differed from propranolol by preserving renal perfusion.

Adolescent↗
PubMed1986

Renal hemodynamic effects of tertatolol compared with those of propranolol in the conscious dog.

Experiments were performed in which the effects of two beta-blockers, tertatolol [dl-(hydroxy-2'-t-butyl-amino-3'-propyloxy)-8-thiochroman hydrochloride] and propranolol, on mean arterial pressure (MAP), heart rate (HR), and renal function were studied in the conscious sodium-replete dog. In all experiments renal function was evaluated from the effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) assessed respectively by measurement of p-aminohippurate and creatinine clearances. These parameters were measured during two 30-min control periods, after which two further measurements were performed over a similar time period, after intravenous administration of either propranolol (0.5 mg X kg-1; n = 8) or tertatolol (0.05 mg X kg-1; n = 8), these two doses being of equivalent beta-adrenoceptor antagonist activity. Administration of propranolol and tertatolol did not change MAP but induced a significant and comparable decrease in HR. After propranolol a significant decrease in ERPF was observed, without any change in GFR or sodium excretion. In contrast, administration of tertatolol resulted in no modification of ERPF, a slight but significant increase in GFR, and a significant increase in sodium and potassium excretion. These results suggest that tertatolol and propranolol though acting similarly on systemic parameters have different effects on renal hemodynamics in the conscious dog.

Adrenergic beta-Antagonists↗
PubMed1986

Tertatolol preserves renal perfusion in patients with arterial hypertension after head injury.

Tertatolol is a noncardioselective beta-adrenergic blocking agent without partial agonist activity. Its central and renal hemodynamic effects were compared to those of an equipotent dosage of propranolol in two groups of 10 patients each who developed arterial hypertension and a hyperdynamic circulatory state after head injury. After tertatolol, 5 mg orally, mean arterial blood pressure was unaffected, heart rate decreased by 22% (p less than 0.01) and cardiac index by 24% (p less than 0.01) while renal blood flow remained unchanged (-5%; not significant) so that the renal fraction of cardiac index was increased by 22% (p less than 0.05). After propranolol, 160 mg orally, mean arterial blood pressure was not modified, heart rate decreased by 12% (p less than 0.01), cardiac index by 16% (p less than 0.01) and renal blood flow by 17% (p less than 0.01) so that the renal fraction of cardiac index remained unchanged (-3%; not significant). Tertatolol is a potent beta-blocking agent comparable to propranolol apart from the fact that it preserves renal perfusion; this peculiar effect is related to a redistribution of the reduced cardiac output to the benefit of the kidney.

Adolescent↗