Antihypertensive Effect Of Propranolol Research Articles

Propranolol and atenolol inhibit norepinephrine spillover rate into plasma in conscious spontaneously hypertensive rats

Radiotracer techniques capable of measuring norepinephrine clearance and spillover rate into plasma were used to test the hypothesis that the antihypertensive effects of propranolol and atenolol in conscious spontaneously hypertensive rats are associated with an inhibition of norepinephrine release from postganglionic sympathetic neurons. The 10%-15% fall in mean arterial pressure produced over 4 h by propranolol (1, 3.3 and 10 mg/kg, s.c.) and atenolol (1, 3.3 and 10 mg/kg, s.c.) was not dose-related, and only the largest dose of propranolol caused a significant bradycardia. Each dose of atenolol significantly lowered heart rate. The decrease in blood pressure caused by propranolol and atenolol was not related to the decrease in heart rate. Both propranolol and atenolol inhibited norepinephrine clearance by 12% to 16%. The 1 mg/kg doses of propranolol and atenolol significantly suppressed norepinephrine spillover rate by 21% and 32%, respectively, at 4 h postinjection. As the dose of propranolol was increased, the inhibition of norepinephrine spillover was reversed as plasma epinephrine concentration rose by 125%. The suppression of norepinephrine spillover rate caused by atenolol was more persistent but did diminish after the 10 mg/kg dose, when plasma epinephrine concentration was elevated by 55%. Both drugs suppressed plasma renin concentration, but the inhibition of norepinephrine spillover rate by propranolol and atenolol was not related to the fall in plasma renin concentration. By comparison, treatment with the adrenergic neuron blocking agent bretylium (5, 10, 20 and 40 mg/kg, s.c.) elicited a dose-related vasodepression with no change in heart rate or plasma renin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Antihypertensive effect and degree of beta-adrenoceptor blockade after short-term and semi-chronic propranolol therapy.

In patients with normal-renin, mild (n = 6) or moderate (n = 6) hypertension, the antihypertensive effects of propranolol (80 mg/day) for 1 day or for 2 weeks were evaluated in relation to the degree of beta-adrenoceptor blockade induced. A significant and similar fall in systolic blood pressure was observed after 1 day and 2 weeks on propranolol in both groups of patients. In contrast, diastolic blood pressure showed only a minor decrease after 1 day of therapy (-2 +/- 2 and -3 +/- 1 mm Hg) but a significant drop (-7 +/- 3 and -9 +/- 3 mm Hg) after 2 weeks in the mild and moderate hypertension groups, respectively. Plasma propranolol levels and decreases in resting heart rate and PRA were similar after 1 day and 2 weeks of treatment. Isoprenaline dose-response curves for systolic and diastolic blood pressure, heart rate and PRA showed similar parallel shifts after 1 day and 2 weeks of treatment. The effect of graded bicycle exercise on these parameters were also similarly blunted. These results indicate that over time, systolic blood pressure decreases rapidly whereas diastolic blood pressure shows a delayed fall following initiation of low-dose propranolol therapy, despite the same degree of beta-adrenoceptor blockade.

Antihypertensive effect of propranolol in conscious spontaneously hypertensive rats: central hemodynamics, plasma volume, and renal function during beta-blockade with propranolol.

In order to obtain a better insight into the hemodynamic changes during beta-blockade, we measured central hemodynamics, plasma volume, and renal function during both acute and long-term beta-blockade in conscious spontaneously hypertensive rats (SHR). Acutely, both 1 and 5 mg/kg propranolol immediately decreased heart rate (HR) and cardiac output (CO). However, total peripheral resistance (TPR) rose sharply, thus preventing mean arterial pressure (MAP) from falling during the first hours after injection. After 4 h TPR had returned to control values and, because CO was still reduced, MAP was lowered. This decrease of MAP persisted for more than 20 h. During 5-day infusion of propranolol (5 mg/kg/day) CO fell on the 1st day and remained lowered during the 5-day period. MAP was lowered from the second day onward. Despite the reduced CO and MAP, plasma volume (PV) did not increase during the 5-day infusion. Acute injection of 5 mg/kg/day did, however, result in a decreased PV at 1 h postinjection. In this time span central venous pressure remained unchanged. Quantitation of water and sodium excretion revealed an immediate diuresis and natriuresis after acute administration of propranolol. This occurred despite a reduced glomerular filtration rate and effective renal plasma flow, as quantitated by indicator clearance methods. We conclude that propranolol reduced tubular sodium reabsorption, possibly through blockade of tubular beta-receptors. This effect may be essential for the long-term antihypertensive efficacy of beta-blockers because it prevents sodium and water retention in a state of reduced MAP and CO.

Propranolol-induced alterations in the pathophysiology of spontaneously hypertensive rats

Male and female, spontaneously hypertensive rats (SHR) were treated with propranolol (14 weeks) when they became 1, 4 and 8 months old prior to, during the steep ascent, and when severe high blood pressure becomes established. Propranolol prevented the usual increase in blood pressure at an early age but did not effectively lower blood pressure at all age levels. Propranolol-treated SHR manifested marked alterations in pituitary, adrenal, thymus, heart and gonadal weights. Despite progressively increasing hyperlipidemia and hyperglycemia, there were no significant differences between lipid, glucose, BUN, or serum enzyme levels in treated vs nontreated SHR. Circulating aldosterone and corticosterone levels were reduced in propranolol-treated SHR. Male SHR, treated or untreated, developed severe cardiovascular-renal lesions when they became 8 months old; none of the female SHR manifested any pathologic changes. It is suggested that the anti-hypertensive effects of propranolol were partially mediated by hormonal as well as by hemodynamic mechanisms.

Relationship of propranolol pharmacokinetics to antihypertensive effect and beta-adrenergic blockade in the treatment of hypertension.

The pharmacokinetics of propranolol in 16 hypertensive patients was compared after the first oral dose of 80 mg and during chronic treatment with 80 mg bd. The degree of beta-adrenergic blockade was estimated by the reduction in maximal exercise heart rate. No significant change in plasma half-life occurred and there was no correlation between the mean steady-state propranolol concentration and beta-adrenergic blockade or antihypertensive effect. A linear relationship was observed between the decrease in blood pressure and the reduction in heart rate during maximal exercise. Therefore, the antihypertensive effect of propranolol can be explained by it peripheral beta-adrenergic blocking properties.

Effect of propranolol on total exchangeable body potassium and total exchangeable body sodium in essential hypertension.

Total exchangeable body potassium (KE) was determined in fifteen patients with essential hypertension, and total exchangeable body sodium (NaE) in ten, before and after propranolol administration for 2-3 months. Blood pressure was reduced; serum potassium increased, but KE was unchanged. Serum sodium and NaE were unaffected during therapy. It is concluded that the increase in serum potassium during propranolol treatment could not be attributed to potassium retention, but is possibly due to a displacement from the intra- to the extracellular fluid compartment. The antihypertensive effect of propranolol could not be related to changes in NaE.

Role of sodium intake in the antihypertensive effect of propranolol.

Twelve hypertensive patients had measurements of body weight, blood pressure, plasma renin activity, and plasma volume during periods of normal sodium intake and acute sodium depletion. After receiving propranolol orally for four to 14 weeks, repeat measurements were obtained under identical conditions of sodium intake. During normal sodium intake, propranolol therapy was associated with a decrease in plasma renin activity, a variable tendency to an increase in body weight and plasma volume, and a decrease in mean arterial pressure of 5 mm Hg (NS). During sodium restriction, blood pressure was decreased significantly from that observed during normal sodium intake and propranolol added a further significant decrease of 8 mm Hg (P less than .01). Blood pressure reductions obtained with sodium depletion and acute diuretic therapy were approximately the same with or without propranolol. The increase in plasma renin activity expected with sodium depletion and diuretic therapy was not blunted by propranolol.

Hemodynamic and Plasma Renin Effects of Propranolol in Essential Hypertension

Hemodynamics and plasma renin activity were measured in 20 ambulatory hospital inpatients with untreated mild to moderate essential hypertension. The control measurements were made after a period of four to seven days just on a diet containing 10 mEq sodium per day. The measurements were repeated following a week of oral propranolol hydrochloride therapy plus the low salt diet. Heart rate (P less than .001), mean arterial pressure (P less than .001), cardiac output (P less than .05), and plasma renin activity (P less than .05) were reduced in the majority of these patients following propranolol therapy but stroke volume increased (P less than .05). Corrected ejection time and total peripheral resistance did not show significant change. The antihypertensive effect of propranolol could not be related to its hyporeninemic effect or to the fall in cardiac output. Under the experimental conditions of this study, no single parameter, either hemodynamic or plasma renin activity, was predictive of a definite antihypertensive response to propranolol therapy.

Anti-Hypertensive Effect of Propranolol and Spironolactone in Relation to Plasma Angiotensin II

Anti-Hypertensive Effect of Propranolol and Spironolactone in Relation to Plasma Angiotensin II

Drug therapy: Propranolol.

IT is almost 10 years since the beta-adrenergic blocking drugs were reviewed in the pages of this journal.1 Although the clinical indications for the administration of propranolol have changed surprisingly little, it has taken some time for its use to become firmly established. It is now officially approved for use in sinus tachycardia, arrhythmias and obstructive cardiomyopathy and, more recently, in the treatment of angina pectoris. The addition of this last indication and the known antihypertensive effects of propranolol, which are at present under review, make it likely that the drug will enjoy more widespread application in the United States. . . .

Effect of propranolol on the blood pressure of normotensive and pinealectomized hypertensive rats.

The antihypertensive effect of propranolol on pinealectomy-induced hypertension was studied in male rats. Pinealectomized hypertensive and unoperated normotensive rats were treated with (±)-propranolol · HCl twice a day p.o. for 20 days, the total daily dose being 5 or 50 mg/kg. The blood pressure of unanaesthetized rats was measured by a tail cuff method about 3 h after the first half of the daily dose on the first, 6th and 16th day of treatment. In unoperated rats both doses of propranolol induced an elevation of blood pressure throughout the experimental period, the mean increase being 5–16 mm Hg. In pinealectomized rats propranolol did not affect the blood pressure on the first day of the treatment, but the higher dose lowered the blood pressure on the 6th day from 148±2 to 137±3 mm Hg, and on the 16th day from 144±2 to 127±3 mm Hg. The lower dose of propranolol lowered the blood pressure only on the 16th day of the treatment. In contrast to the delay in the onset of the antihypertensive action of propranolol, stress-induced tachycardia was antagonized as early as 1 h after the first administration of the drug. In pinealectomized rats plasma renin activity was slightly increased. On the 20th day of treatment plasma renin activity was not significantly affected by either dose of propranolol in unoperated or pinealectomized rats. In an acute experiment propranolol (50 mg/kg p.o.) clearly lowered plasma renin activity in both unoperated and pinealectomized rats within 1 h. A single dose of 5 mg/kg of propranolol influenced plasma renin activity in neither group of rats. Since there are beta-adrenoceptor antagonists which block cardiac beta-receptors and which lower plasma renin activity without exerting an antihypertensive effect, it is concluded that the antihypertensive effect of propranolol in pinealectomized rats is not attributable to a blockade of the cardiac beta-receptors or to a decrease of plasma renin activity.