Significant Hypotensive Effect Research Articles

Effect of the application of acetazolamide soaked contact lenses on intraocular pressure of rabbits

Topical application of acetazolamide has no known effect on intraocular pressure (IOP). We tried to detect the hypotensive effect on IOP of acetazolamide soaked onto soft contact lenses (CL). We applied CLs soaked in either 1%, 3%, or 5% acetazolamide solution onto one eye of 29 rabbits while the contralateral eye served as a control. There was an average 32% reduction of IOP amongst all acetazolamide applied eyes, and an average 19% reduction of IOP amongst all control eyes. Amongst the 1% acetazolamide-CL applied eyes there was a mean 37% reduction of IOP, amongst the 3% acetazolamide-CL applied eyes a mean 36% reduction, amongst the 5% acetazolamide-CL applied a mean 30% reduction, and a mean 19% reduction in control eyes. The longest period of IOP reduction followed the application of 1% acetazolamide-CLs, probably owing to improved drug corneal penetration at this concentration. Our results reveal that the application of acetazolamide soaked soft CLs has a significant hypotensive effect on IOP in both the applied and contralateral control eyes of rabbits.

A study of some potential correlates of the hypotensive effects of prolonged submaximal exercise in normotensive men.

This study was undertaken (1) to examine the relation of plasma catecholamine and insulin levels to the blood pressure response during and after submaximal exercise, (2) to verify whether the blood pressure response to an epinephrine infusion is associated with the blood pressure response to a prolonged submaximal exercise, and (3) to study some potential correlates of the hypotensive effect of prolonged aerobic exercise. Nine normotensive young men (mean age 22.0 +/- 1.4 years) were subjected to a 1-h epinephrine infusion protocol and a 1-h submaximal exercise test on a cycle ergometer. The two tests were performed 1 week apart. The physiological and hormonal responses observed during the submaximal exercise test were generally greater than those observed during the epinephrine infusion test. Blood pressure responses in both tests showed no significant association with changes in plasma insulin levels. Changes in plasma norepinephrine concentration were positively correlated with changes in systolic blood pressure during the submaximal exercise test but not during the epinephrine infusion. Results also showed that the blood pressure response to epinephrine infusion was not correlated with the blood pressure response to submaximal exercise. However, post-exercise and post-infusion systolic blood pressure responses (differences between "post-test" and "resting" values) were significantly associated (r = 0.81, p less than 0.01). In addition, a significant hypotensive effect of submaximal exercise was observed for both systolic and diastolic blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Haemodynamic, metabolic and endocrine effects of short-term dexfenfluramine treatment in young, obese women

Seventeen normotensive, premenopausal women were treated with the 5-hydroxytryptamine-reuptake inhibitor dexfenfluramine 30 mg per day, for 4 days in a randomised double-blind, cross-over, placebo controlled trial. Energy intake was held constant during the study as the aim was to study the endocrine and metabolic effects of dexfenfluramine dissociated from its weight-lowering properties. Body weight, blood glucose, plasma insulin, cholesterol triglycerides and C-peptide after an overnight fast and during an oral load of 100 g glucose did not change after dexfenfluramine compared to placebo. Supine and standing systolic and diastolic blood pressures were significantly decreased, while heart rate remained unchanged. Plasma noradrenaline and plasma renin were markedly reduced by dexfenfluramine, and cortisol, beta-endorphin and thyroid hormones were not changed. Thus, dexfenfluramine has a significant hypotensive effect in normotensive, obese women after 4 days of treatment, independent of a negative energy balance. This was associated with decreased circulating plasma noradrenaline, indicating decreased sympathetic nerve activity. Dexfenfluramine may be a candidate drug for longer-term trials in the treatment of primary hypertension associated with obesity.

Effects of aminoguanidine on pre- and post-irradiation regional cerebral blood flow, systemic blood pressure and plasma histamine levels in the primate

Exposure to ionizing radiation causes hypotension, cerebral ischemia and release of histamine (HA). To investigate the relationship among these three responses, rhesus monkeys (Macaca mulatta) received aminoguanidine (AG) (1 mg/kg), then were given either 50 Gy whole-body irradiation or sham-irradiation. Monkeys receiving AG had lower mean arterial blood pressure (MABP) than saline-treated controls. Compared to controls, rCBF was lower in irradiated monkeys but pre-treatment with AG did not influence this effect. Among untreated, irradiated monkeys, HA levels were increased only at two minutes post-irradiation, but among AG-treated, irradiated monkeys, HA levels were higher at all times postirradiation. Radiation-induced release of HA may be associated with radiation-induced hypotension and reduced rCBF, but failure of AG to alter rCBF suggests that released HA may not be the sole mediator of these effects. Because elevations in plasma HA are probably due to HA derived from degranulation of mast cells, release of other bioactive substances from mast cells may also influence these cardiovascular effects. Surprisingly, in sham-irradiated monkeys, AG alone had a slight but significant hypotensive effect.

The Effects of Nisoldipine, Diltiazem, Nifedipine, and Verapamil on Hemodynamic Parameters and Red Blood Cells-Platelet Interactions in Patients with Arterial Hypertension

In 80 patients with moderate hypertension the effects of nisoldipine 10 mg b.i.d., nifedipine 10 mg and 20 mg t.i.d., diltiazem 60 mg and 120 mg t.i.d., and verapamil 40 mg q.i.d. (all after single dose and 14 days' treatment) on blood pressure; hemodynamic parameters (cardiac output, stroke volume, left ventricular ejection fraction, and total peripheral resistance); and red blood cell and platelet functional state parameters (platelet aggregation, erythrocytal mechanical resistance, and free hemoglobin and ADP levels in plasma) were studied. All of the drugs studied in doses mentioned produced statistically significant hypotensive effects. Nifedipine 20 mg and nisoldipine 10 mg produced the most peripheral vasodilatator activity after a single dose and chronic treatment. Diltiazem had the same effect only in doses of 120 mg and after chronic treatment. However, all the drugs significantly normalized the red blood cell and platelet functional state disturbances in 70-80% of patients with moderate hypertension, even 2 h after a single dose. Disaggregation effect was parallel to clinical improvement. These data make it possible to predict the individual response of most patients to antihypertensive drugs on the basis of acute pharmacological tests, with determination of disaggregation effect.

The Effects of Nisoldipine, Diltiazem, Nifedipine, and Verapamil on Hemodynamic Parameters and Red Blood Cells-Platelet Interactions in Patients with Arterial Hypertension

In 80 patients with moderate hypertension the effects of nisoldipine 10 mg b.i.d., nifedipine 10 mg and 20 mg t.i.d., diltiazem 60 mg and 120 mg t.i.d., and verapamil 40 mg q.i.d. (all after single dose and 14 days' treatment) on blood pressure; hemodynamic parameters (cardiac output, stroke volume, left ventricular ejection fraction, and total peripheral resistance): and red blood cell and platelet functional state parameters (platelet aggregation, erythrocytal mechanical resistance, and free hemoglobin and ADP levels in plasma) were studied. All of the drugs studied in doses mentioned produced statistically significant hypotensive effects. Nifedipine 20 mg and nisoldipine 10 mg produced the most peripheral vasodilatator activity after a single dose and chronic treatment. Diltiazem had the same effect only in doses of 120 mg and after chronic treatment. However, all the drugs significantly normalized the red blood cell and platelet functional state disturbances in 70–80% of patients with moderate hypertension, even 2 h after a single dose. Disaggregation effect was parallel to clinical improvement. These data make it possible to predict the individual response of most patients to antihypertensive drugs on the basis of acute pharmacological tests, with determination of disaggregation effect.

Eicosanoids as a new class of ocular hypotensive agents. 3. Prostaglandin A 2-1-isopropyl ester is the most potent reported hypotensive agent on feline eyes

It has been shown that prostaglandin A 2 (PGA 2) is a more potent ocular hypotensive agent in cats than other PG free acids. We report here that significant IOP reduction can be achieved in normotensive cat eyes with the use of even lower doses of PGA 2-1-isopropyl ester (PGA 2-IE) than with PGA 2, PGF 2α-1-isopropyl ester (PGF 2α-IE), or any other known ocular hypotensive agent. Furthermore, single applications of 0·5 μg of PGA 2-IE maintain significant IOP reductions for at least 24 hr. This hypotensive effect is enhanced during the first 3–5 days of daily treatment. Significant IOP reductions were maintained for several months as long as PGA 2-IE was applied daily or at least once every 48 hr. None of the cats manifested signs of discomfort in response to treatment with doses ranging from 0·10 to 1·25 μg of PGA 2-IE. Moreover, the extent of anterior chamber flare was less than that typically observed after the topical application of hypotensive doses of PGE 2, PGD 2, PGF 2α, or the esters or tromethamine salt of PGF 2α. Although it is possible that the human eye would respond differently to PGs of the A type, the results of these studies suggests that PGA 2-IE or other esters of derived PGs of the A type, and probably the B type, may offer significant therapeutic advantages over the PGF 2α tromethamine salt and PGF 2α-IE, which have been shown to exert significant hypotensive effects on normal and glaucomatous human eyes.

The use of carvedilol in elderly hypertensive patients

Carvedilol, a beta-blocking drug with vasodilator activity, has been used in 4 studies in 107 elderly patients with essential hypertension and has reduced blood pressure effectively. In the first study the pharmacokinetics and clinical response were compared between 21 patients greater than 65 years of age and 8 patients aged 35-50 years). The peak blood levels, time to maximal concentration, area under the curve, half-life and trough level of the drug with chronic administration did not differ. The clinical responses to the drug were similar, with a greater fall in systolic blood pressure in the older group. However the initial systolic blood pressure in the older group was higher. Carvedilol was compared with metoprolol, pindolol and nitrendipine in elderly patients. The responses to carvedilol were at least equal to those obtained with the other drugs. Control was achieved in the three studies with once-daily therapy. There was no significant postural hypotensive effect. A feature of all studies was the large number of patients who responded to carvedilol. The side-effect profile of the drug was acceptable; headache and dizziness were more common than with placebo or the comparison drugs and were frequently associated. There were no adverse biochemical effects and the lipid profile was not altered. Carvedilol is an effective antihypertensive drug that lowers blood pressure equally well in the young and the old.

Comparison of Sublingual Captopril and Sublingual Nifedipine in Hypertensive Emergencies

AbstractHypertensive crises require immediate therapy, usually by parenteral drug administration. Sublingual nifedipine has been shown to be highly effective. However, the blood pressure fall following nifedipine is frequently associated with side-effects. The use of sublingual captopril has recently been indicated in hypertensive crisis, assuming that by this route, there would be a faster absorption and thus a more rapid effect on blood pressure than with the oral route. To verify this hypothesis, we have compared the hypotensive effects of sublingual nifedipine and sublingual captopril in 52 patients with hypertensive emergencies: 25-mg captopril and 10-mg nifedipine were administered sublingually to 28 and 24 patients, respectively. Blood pressures and heart rates were continuously measured up to 240 min postdose. A significant (P<0.001) hypotensive effect of both sublingual captopril and nifedipine therapy occured at 5 min and persisted for 240 min. Heart rates increased with nifedipine, but decreased with captopril. We observed no side-effects in the captopril group, but flushing, tachycardia and headache were observed in 6 patients in the nifedipine group. We conclude that sublingual captopril is effective in patients with hypertensive emergencies and that captopril may be an excellent alternative to sublingual nifedipine in the urgent treatment of hypertensive crisis.

Comparison of sublingual captopril and sublingual nifedipine in hypertensive emergencies.

Hypertensive crises require immediate therapy, usually by parenteral drug administration. Sublingual nifedipine has been shown to be highly effective. However, the blood pressure fall following nifedipine is frequently associated with side-effects. The use of sublingual captopril has recently been indicated in hypertensive crisis, assuming that by this route, there would be a faster absorption and thus a more rapid effect on blood pressure than with the oral route. To verify this hypothesis, we have compared the hypotensive effects of sublingual nifedipine and sublingual captopril in 52 patients with hypertensive emergencies: 25-mg captopril and 10-mg nifedipine were administered sublingually to 28 and 24 patients, respectively. Blood pressures and heart rates were continuously measured up to 240 min postdose. A significant (P less than 0.001) hypotensive effect of both sublingual captopril and nifedipine therapy occurred at 5 min and persisted for 240 min. Heart rates increased with nifedipine, but decreased with captopril. We observed no side-effects in the captopril group, but flushing, tachycardia and headache were observed in 6 patients in the nifedipine group. We conclude that sublingual captopril is effective in patients with hypertensive emergencies and that captopril may be an excellent alternative to sublingual nifedipine in the urgent treatment of hypertensive crisis.

Renal vasodilators. The role of the 4-substituent in isoquinolin-3-ol cardiovascular agents: 4-ureido derivatives of isoquinolin-3-ol with selective renal vasodilator properties.

The synthesis and cardiovascular evaluation of a series of isoquinolin-3-ol derivatives bearing a variety of nitrogen substituents (amino, acylamino, carbamate, and ureido) at C-4 are described. Certain of these compounds have a selective renal vasodilating profile and have minimal effects on arterial blood pressure or heart rate when administered intravenously in the instrumented anesthetized dog. The most potent renal vasodilator in the series is 4-(allylureido)-6,7-dimethoxyisoquinolin-3-ol (38), which at a dose of 1.2 mg/kg iv produces a 97% maximal increase in renal blood flow without significant hypotensive or chronotropic effects. Structure-activity observations on the nature of the 4-substituent and the alkoxy substitution pattern in the aromatic ring of the isoquinolinol nucleus are discussed.

The feasibility of low dose barbiturate administration by intra-carotid infusion to achieve EEG burst suppression--a preliminary report.

More than 10 years have elapsed since the introduction of high dose barbiturate administration in the management of patients with severe head injuries. Barbiturate therapy became an accepted method of treatment for increased intracranial pressure when other measures fail. One of the major limiting factors in the use of high dose barbiturate therapy is its significant hypotensive effect on the systemic arterial blood pressure. In seeking ways and means of minimising this hypotensive effect, we designed a study in which the systemic administration of barbiturates is avoided and replaced by selective perfusion of the concerned hemisphere with the drug utilising the intra-carotid route. Twenty-two rats, divided into two groups, were used in the study. Since monitoring of electroencephalographic (EEG) burst suppression serves as a good indicator of the lowest level of cerebral metabolic activity, we used this as the method for determining the desired endpoint of sodium amytal administration in both groups of animals. Group I, the intravenous group, consisted of eleven animals who received sodium amytal intravenously until burst suppression on the EEG was documented. Group II, the intra-carotid group, comprised eleven animals who received intra-carotid sodium amytal until EEG burst suppression was induced. In the intravenous group, a mean dose of 35 mg/kg of sodium amytal was administered before EEG burst suppression was achieved. This dose, however, was accompanied by an almost 50% reduction in systemic blood pressure compared to the pretreatment level. The intra-carotid group required a mean dose of 3.8 mg/kg sodium amytal and this was accompanied by only minor changes in systemic arterial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)

Eicosanoids as a new class of ocular hypotensive agents.: 1. The apparent therapeutic advantages of derived prostaglandins of the A and B type as compared with primary prostaglandins of the E, F and D type

The classic primary prostaglandins (PGs), as well as some of their analogs and derivatives, are potent ocular hypotensive agents. The present studies show that A and B PGs, which are derived from PGs of the E type by dehydration and isomerization, have a much greater ocular hypotensive potency than the primary PGs of the E, F or D type. A single application of 5 micrograms of PGA2 to the cat eye in a 25-microliters volume of aqueous vehicle solution yielded a greater and more prolonged ocular hypotensive effect than as much as 100 micrograms of topically applied PGF2 alpha. As little as 1 microgram of PGA2 had a significant ocular hypotensive effect that was enhanced by three or more consecutive daily applications of the same dose. This IOP reduction, which remained significant for several days after the last of 10 daily treatments, was not associated with biomicroscopically detectable flare or invasion of the anterior chamber by cells. Although PGF2 alpha and, to a much lesser extent, PGE2 have a miotic effect in cats, PGs of the A and B type did not cause significant miosis even at doses 50- to 100-fold greater than the minimum dose required to yield significant ocular hypotension. PGA2 retained its ocular hypotensive potency when stored in an aqueous solution at room temperature for four months. The conjunctival hyperemia caused by 5 micrograms or 10 micrograms of A or B type PGs on rabbit eyes was milder and shorter in duration than that caused by the same doses of PGE2 or PGF2 alpha. These findings suggest that derived PGs, especially PGs of the A type, may have a therapeutic advantage over primary PGs for the treatment of ocular hypertension and glaucoma.

Rectal administration of nifedipine: haemodynamic effects and pharmacokinetics in hypertensives.

The haemodynamic effects and pharmacokinetics of nifedipine suppositories, used mainly for hypertensive emergencies, were studied in 10 severely hypertensive patients. Following rectal administration, significant hypotensive effects occurred after 0.5 h and lasted until 7 h after administration. The mean (+/- SE) maximum decreases in systolic and diastolic blood pressures 1.5 h after administration were: systolic, 61.8 +/- 7.9 mmHg (P less than 0.001); and diastolic, 30.8 +/- 4.0 mmHg (P less than 0.001). No serious side-effects were reported and heart rate did not change significantly. Mean nifedipine concentration in the blood peaked at 52.4 ng/ml, 1 h after administration and, after 7 h, was still 14.3 ng/ml which is higher than the minimum plasma concentration required for hypotensive effects to occur. There was a close correlation between nifedipine concentration in the blood and hypotensive effects. These results indicate that rectal administration of nifedipine should be regarded as a useful alternative treatment in hypertensive emergencies.

Effects of Betaxolol, a New Beta 1 Selective Blocker, on Canine Ventricular Arrhythmias

Antiarrhythmic effects of a new beta 1 selective adrenoceptor blocker, betaxolol, were examined in comparison with those of atenolol using two canine ventricular arrhythmia models (adrenaline arrhythmia and digitalis arrhythmia). Both betaxolol and atenolol suppressed adrenaline arrhythmia, and the minimum effective plasma concentration of betaxolol for this arrhythmia model was determined to be less than 10 ng/ml. However, on digitalis arrhythmia, both beta blockers were ineffective, even though the high doses used in these experiments, 3 mg/kg for betaxolol and 5 mg/kg for atenolol, showed significant hypotensive effects. The present results suggest that betaxolol and atenolol may be expected to be clinically effective on arrhythmias related to increased sympathetic tone.

Effects of betaxolol, a new beta 1 selective blocker, on canine ventricular arrhythmias.

Antiarrhythmic effects of a new beta 1 selective adrenoceptor blocker, betaxolol, were examined in comparison with those of atenolol using two canine ventricular arrhythmia models (adrenaline arrhythmia and digitalis arrhythmia). Both betaxolol and atenolol suppressed adrenaline arrhythmia, and the minimum effective plasma concentration of betaxolol for this arrhythmia model was determined to be less than 10 ng/ml. However, on digitalis arrhythmia, both beta blockers were ineffective, even though the high doses used in these experiments, 3 mg/kg for betaxolol and 5 mg/kg for atenolol, showed significant hypotensive effects. The present results suggest that betaxolol and atenolol may be expected to be clinically effective on arrhythmias related to increased sympathetic tone.

Prolactin and Blood Pressure Responses to Perphenazine in Human Subjects: Comparison of the Oral and Intramuscular Routes

Although several phenothiazines are known to stimulate prolactin (PRL) secretion, only chlorpromazine is in general use for this purpose in humans. However, chlorpromazine has severe sedative and hypotensive effects. Therefore, the effects of perphenazine on human PRL release and on blood pressure were evaluated. Perphenazine was administered orally (8mg) and intramuscularly (5mg and 2mg) to determine the optimal route and dose for evaluating PRL release. The postural hypotensive effect of perphenazine was evaluated with the 2mg intramuscular (IM) dose. The mean time of peak PRL response (hr +/- SD) was significantly shorter (p less than 0.05) for the 5mg IM (1.7 +/- 0.4) than the oral (4.5 +/- 0.6) route. Also, the mean ratio of peak/baseline PRL was significantly greater for the 5mg IM (8.87 +/- 5.69) than the oral (5.12 +/- 2.90) route. The major side-effect produced by perphenazine was drowsiness, which was moderate to severe with the 5mg IM dose. A lower IM dose (2 mg) retained PRL releasing activity, reduced drowsiness, and did not produce hypotension. For clinical testing, intramuscular perphenazine is preferred over oral perphenazine because of the shorter latency period and the higher PRL levels. Intramuscular perphenazine (2 mg) is preferred to chlorpromazine since it did not produce a clinically significant hypotensive effect. This is the first report on the dynamic responses of PRL and blood pressure to intramuscular perphenazine in humans.

Investigations on West African medicinal plants

Abstract

Evidence against the role of calcium deficiency in genetic hypertension.

Epidemiological studies suggest an association between reduced calcium uptake and hypertension, while clinical trials and rat experiments indicate a small but significant hypotensive effect with oral calcium supplements. These data imply that calcium deficiency has a role in genetic hypertension. We reasoned that if the hypothesis is correct, the hypertension should be aggravated by further reducing calcium balance but attenuated by augmenting calcium balance. We tested this hypothesis by evaluating the blood pressure response in spontaneously hypertensive rats (SHR) as calcium balance was decreased by dietary restriction of calcium or increased by supplementation with magnesium or 1 alpha, 25-dihydroxycholecalciferol (calcitriol). A low calcium diet within the physiological range did not accentuate the hypertension in SHR during the 11 weeks of treatment, even though calcium balance was reduced by half. Similar results were obtained with dietary calcium restriction in parathyroidectomized SHR, which excludes any offsetting effects of changes in parathyroid hormone levels. Conversely, 7 weeks of a high magnesium diet, which increased calcium balance without reducing PO4 balance, did not correct the hypertension of SHR. Similarly, long-term administration of calcitriol failed to reduce the blood pressure of parathyroidectomized SHR and normotensive Wistar-Kyoto (WKY) controls, despite the presence of increased serum calcium levels comparable to those produced by oral calcium loading. Finally, external calcium balance was measured directly in 25-day-old, prehypertensive SHR. As a result of the increased calcium absorption and reduced calcium excretion, SHR retained more calcium than did the normotensive WKY, which directly refutes the existence of calcium deficiency at this normotensive stage. These data do not support the role of calcium deficiency in genetic hypertension.

Alpha-human atrial natriuretic polypeptide-induced rise of plasma and urinary cyclic 3'5'-guanosine monophosphate concentration in human subjects.

Synthetic alpha-hANP was infused into 8 normotensive, euvolemic volunteers to examine the effects on plasma and urinary cyclic-GMP. The dose given and duration of alpha-hANP (0.1 micrograms/kg/min, 20 min) led to the significant diuresis, saliuresis and hypotensive effects in each subject. The mean plasma cyclic-GMP concentration was clearly elevated at 5 min after infusion and attained 8 fold of the mean basal concentrations by the end of infusion. The mean urinary cyclic-GMP excretion rate also showed 3.5 fold increases of the basal excretion rate with synthetic alpha-hANP administration (before loading: 0.69 +/- 0.22 p moles/g creat., after loading: 2.85 +/- 0.28 p moles/g creat.). However, there was no apparent change on plasma or urinary cyclic-AMP during the infusion. The result clearly demonstrated that synthetic alpha-hANP selectively induces the cyclic-GMP in concomitant with the marked diuretic, natriuretic and hypotensive effects in human subjects.