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Biomedical subjects

I Gavras

Publications and source records attributed to I Gavras.

At least 163 records · Page 9Linked to original sources
PubMedDate not supplied

Effect of a new beta-adrenergic blocker, l-bunolol, on blood pressure and on the renin-aldosterone system.

The antihypertensive effect of a new beta-adrenergic receptor blocker, l-bunolol, was evaluated in 11 hospitalized hypertensive patients of whom four belonged to the high-renin, five to the normal-renin, and two to the low-renin subgroup. There was a significant decrease in blood pressure in most patients, often to normal. Moreover, plasma renin levels were nearly always markedly suppressed, and this suppression preceded the fall in blood pressure. While most high and normal renin patients responded, the numbers of patients within each subgroup were too small to correlate the blood pressure responses with changes in renin levels. There was a significant induced decrease in aldosterone excretion, which usually paralleled the renin suppression. Pulse rate was also consistently reduced during treatment. No weight gain was observed, except in one patient who developed overt congestive cardiac failure. No other side effects were recorded. Ii is concluded that l-bunolol is another beta-blocking drug with significant antihypertensive action. It was found to be effective in cases that were resistant to propranolo. It is well tolerated and safe to use, provided that early evidence of fluid retention is sought for and treated immediately.

Adult↗
PubMedDate not supplied

Effect of nadolol in treatment of hypertension.

Nadolol, a new beta-adrenergic blocking agent, was administered orally in gradually increasing single daily doses to 13 hospitalized patients with essential hypertension. Maximal doses ranged from 200 to 480 mg/day. Blood pressure was reduced in nine patients and heart rate was decreased in 11 patients. The decrease in blood pressure was either partial or temporary in five of the nine patients who responded. Concomitant administration of the diuretic chlorthalidone decreased blood pressure in a previously unresponsive patient. Nadolol effectively inhibited isoproterenol-induced tachycardia and decreased cardiac output by 18 per cent. Plasma renin activity and plasma aldosterone concentration were not changed significantly by the treatment. Body weight was not altered significantly. Blood pressure response was independent of the pretreatment renin levels or the change in renin induced by nadolol; it was also independent of the changes in cardiac output and heart rate but was more pronounced in patients with milder baseline hypertension. The decline in serum concentration of nadolol was consistent with the drug's reported half-life of 12.2 hours. The results indicate that single daily doses of nadolol alone can reduce blood pressure significantly with minimal cardiodepressant effects and no important side effects. The effectiveness of nadolol may be enhanced by the addition of a diuretic.

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Effect of pindolol on blood pressure, plasma renin activity, and catecholamines in hypertensive patients.

The effects of 45 mg pindolol daily on blood pressure, heart rate, plasma renin activity, and plasma catecholamines were assessed on 11 hospitalized hypertensive patients. Blood pressure decreased significantly after nine days of treatment, but heart rate remained unchanged. Plasma renin activity was in the same average range before and during treatment, with individual values variably increasing, decreasing, or remaining unchanged. Blood pressure changes were independent from the baseline level of plasma renin activity or the change in renin activity observed during treatment. Plasma epinephrine and norepinephrine levels also remained unchanged during treatment. Lack of change in heart rate and hormonal levels may be attributed to the combined effects of the beta-antagonistic and partial agonistic properties of this agent. Thus, pindolol used as monotherapy at this dose significantly lowered blood pressure, but not to normal levels, with only minimal side effects. Because of its combined adrenergic agonistic and antagonistic effects, it may be a preferable alternative to pure antagonists in selected patients.

Adult↗
PubMedDate not supplied

Safety and efficacy of chronic therapy with captopril in hypertensive patients: an update.

Captopril, an orally active angiotensin-converting enzyme inhibitor, has been administered to 81 patients with different types of clinical hypertension. Most of the patients had previously uncontrollable high blood pressure. In order to achieve a satisfactory blood pressure control during long-term captopril therapy, a concomitant decrease in total body sodium was required in more than half of the patients. During our first two years of clinical experience with this new antihypertensive agent, side effects developed in 46.9 per cent of the patients and necessitated the withdrawal of the drug in 23.4 per cent of all patients. Only a few side effects such as hypotensive or syncopal episodes and cold extremities appeared to be due to the chronic blockade of the renin-angiotensin system. The most frequent and the most serious adverse reactions such as skin rash, altered taste, pancytopenia, and pemphigus foliaceus seemed to be specifically drug related. The incidence of cutaneous and taste problems was markedly higher in patients with impaired renal function in whom retention of captopril has been previously demonstrated. This suggests that the occurrence of adverse reactions to captopril could be lowered in the future by using smaller daily doses and by titrating them according to the renal function.

Adolescent↗
PubMedDate not supplied

Pilot study of the effects of the angiotensin-converting enzyme inhibitor CI-906 on patients with essential hypertension.

The effects of two single doses of the new oral nonsulfhydryl angiotensin-converting enzyme (ACE) inhibitor CI-906 on blood pressure and hormone levels are described in eight subjects with essential hypertension. Starting at 0.625 mg, doses were separated by a placebo day and doubled in consecutive patients until the full effect (obtained with 5 and 10 mg) was reached, at which point the remaining patients received the same dosage. All doses, including the smallest, caused ACE suppression to less than 1 per cent of baseline lasting for least 12 hours and remaining below 30 per cent at 48 hours, accompanied by a rise in plasma renin activity (by 10.9 +/- 2.1 ng/ml/hr) and fall in aldosterone (by -12.6 +/- 2.5 ng/100 ml). However, a clinically significant, though partial and short-lived, effect on blood pressure was observed at 2.5 mg. The two highest doses produced similar effects in terms of magnitude of mean blood pressure lowering (by 26 +/- 5 and 25 +/- 2 mm Hg, respectively) and duration (varying from 12 to over 24 hours) regardless of pretreatment renin levels. There was no orthostatic hypotension, tachycardia, or other adverse reaction.

Adult↗
PubMedDate not supplied

Isradipine versus captopril in patients with essential hypertension.

We conducted a double-blind, crossover study comparing the antihypertensive effects of isradipine versus captopril in patients with essential hypertension. Seventeen patients (8 men, 9 women; 6 whites, 11 blacks) completed both phases of the study, which consisted of two 5-week treatment periods separated by 2 weeks of placebo treatment. Each drug was randomly allocated to half the patients as the first drug and half as the second drug they received. Ambulatory blood pressure (BP) monitoring was carried out on the day before treatment and the last day of each active treatment. Both drugs were effective and well tolerated but isradipine was more effective overall than captopril in lowering BP (9.4% vs 3.9%, respectively; P < 0.02). Black patients had significantly higher BP at baseline than white patients; furthermore, black patients responded better to isradipine than to captopril. White patients had a smaller decrease in blood pressure with both drugs than did black patients, but white patients still attained a lower diastolic BP with captopril than did black patients (88 +/- 2 mm Hg vs 96 +/- 9 mm Hg; P < 0.01). There was no correlation between the pretreatment plasma levels of pressor hormones (plasma renin activity, catecholamines, and arginine vasopressin) and the magnitude of BP response to either drug, but the decrease in BP in response to captopril correlated significantly with the increase in plasma renin activity during treatment (r = -.84; P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

A new highly potent antagonist of bradykinin.

We report that the acylation of the N-terminus of [D-Arg0,Hyp3,Thi5,8,D-Phe7]bradykinin, one of the most potent bradykinin antagonists described to date, with 1-adamantane-acetic acid, results in an analogue with more than ten times enhanced potency. The new analogue does not increase the plasma catecholamines, even when administered at doses sufficient to inhibit by more than 90% the vasodepressor response to 250 ng of exogenous bradykinin. This modification suggests new possibilities for the design of even more potent and selective bradykinin antagonists for studying the physiopathology of bradykinin.

Animals↗
PubMedDate not supplied

Role of reactive hyperreninemia in blood pressure changes induced by sodium depletion in patients with refractory hypertension.

Sixteen patients with refractory hypertension were submitted to vigorous sodium depletion while cardiovascular homeostasis was monitored with measurements of hormonal and hemodynamic parameters and repeat saralasin tests. This regimen resulted in a negative sodium balance by an average of 300 mEq. The loss of sodium closely correlated to the decrease of body weight (r = 0.70, p less than 0.005). Blood pressure (BP) decreased from 176/166 +/- 8/3 to 155/109 +/-6/3 mm Hg. There was a significant correlation between percent increments in plasma renin activity (PRA) and the rise in plasma norepinephrine (r = 0.68, p less than 0.05) and a close negative correlation between percent increase in PRA and the ratio of fall in mean blood pressure (MAP) per unit of weight loss (r = -0.73, p less than 0.005). Thus, patients with the least percent increase in PRA demonstrated the greatest fall in BP per unit of weight loss, indicating that relative rather than absolute elevation of renin may be the factor limiting antihypertensive efficacy of sodium depletion. Sodium depletion induced increase in peripheral resistance and decrease in cardiac output, both mostly attributable to relative hyperreninemia. Indeed, the adverse hemodynamic changes were reversed by angiotensin inhibition, during which BP normalized. It is concluded that vigorous sodium depletion complemented by angiotensin blockade or suppression with sympatholytic agents improves management of otherwise refractory hypertension.

Adult↗
PubMedDate not supplied

Interaction of the sympathetic nervous system with vasopressin and renin in the maintenance of blood pressure.

To evaluate the partial contributions and interaction of three vasopressor systems in blood pressure maintenance, nephrectomized rats and rats with intact kidneys were submitted sequentially to catecholamine depletion, elimination of vasopressin's vasoconstrictor action, and (for those with kidneys in situ) angiotensin blockade. Catecholamine depletion decreased blood pressure and stimulated vasopressin levels in all rats, but significantly more so in the anephric ones. Subsequent injection of an antagonist to the vasopressor effect of vasopressin produced a lasting fall of blood pressure in anephric rats, but only transient fall in those with intact kidneys. Infusion of teprotide--an angiotensin converting enzyme inhibitor--in the latter animals also produced transient blood pressure fall, but if this were followed by injection of the vasopressin antagonist, the pressure remained low for several hours. Blood pressure levels were closely correlated with those of plasma catecholamines throughout these maneuvers. Catecholamine levels were inversely correlated with those of plasma vasopressin, which were far greater in anephric rats through both stimulation and accumulation. Plasma renin activity was increasingly stimulated by falling blood pressure after each maneuver in rats with intact kidneys. Thus, it appears that in the resting state the sympathetic nervous system is more involved in the maintenance of blood pressure, whereas vasopressin and renin are important backup mechanisms.

Animals↗
PubMedDate not supplied

Effects of a specific inhibitor of the vascular action of vasopressin in humans.

Experimental evidence indicates that arginine vasopressin (AVP) may contribute to the rise of blood pressure (BP) in hypertension induced by renal failure and sodium overload. We studied the AVP inhibitor [1-(B-mercapto-B,B-cyclopentamethylenepropionic acid)-2-(O-methyl)tyrosine] AVP in 12 normal and seven hypertensive subjects with end-stage renal disease. To test the agent's capacity to block the pressor action of exogenous AVP In humans, we constructed a dose-response curve with AVP doses of 1 to 20 mU/kg, raising BP by up to 30 mm Hg. Subsequently, five volunteers receive intravenous (i.v.) doses of 0.1 mg, and five volunteers received 0.5 mg of the inhibitor. The dose-response curve was then repeated with AVP doses up to 200 mU/kg. Both doses of the inhibitor shifted the curve to the right and downward, with the BP response to 20 mU/kg AVP being inhibited by 23% and 80% respectively. The duration of action of the compound was tested in two additional subjects, and was found to be over 3 hours. We then tested the compound in seven hypertensive patients with end-stage renal failure. Two days before dialysis, patients received a 150 mEq/day Na diet. After an additional Na load of 180 mEq via i.v. saline over 3 hours under constant BP and ECG monitoring, they received an i.v. bolus of 0.5 mg AVP inhibitor. A moderate BP fall occurred in five patients; it was maximal at 45 to 60 minutes and returned to baseline by 70 to 90 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMedDate not supplied

Antihypertensive therapy with MK 421: angiotensin II--renin relationships to evaluate efficacy of converting enzyme blockade.

Nineteen hypertensive patients were treated with increasing doses of the new angiotensin-converting enzyme inhibitor MK 421. Twenty milligrams orally reduced blood pressure from 180/112 +/- 6.8/3.6 (mean +/- SEM) to 160/100 +/- 6.5/3.3 mm Hg (p less than 0.005) while heart rate increased from 75 +/- 2 to 87 +/- 3 beats/min (p less than 0.005). Plasma converting enzyme activity was still markedly reduced 24 h following 2.5, 5, 10, or 20 mg MK 421 p.o. (p less than 0.001). In nine patients treated with 20 mg b.i.d. for up to 10 months, blood pressure was controlled, with the association of hydrochlorothiazide 50 mg q.d. in five. However, 12 to 16 h following the preceding drug administration, plasma angiotensin II and aldosterone were back to base-line levels. Analysis of plasma angiotensin II-renin relationships strongly suggests that converting enzyme blockade is not complete even 4 h after 20 mg MK 421 and starts to wear off already at 12 h. Thus, MK 421 20 mg taken orally twice daily, effectively reduces blood pressure, but does not constantly suppress plasma angiotensin II and aldosterone. Whether its long duration of action makes once daily administration possible has not yet been established.

Adult↗