Dopamine-induced antihypertensive effects and plasma insulin rise are blocked by metoclopramide in labetalol-treated patients.

Eleven patients with moderate to severe hypertension were studied at the Vargas Hospital of Caracas. The patients were pretreated with labetalol, 800 to 1200 mg/day, orally, over a period of 1 week, after which an intravenous infusion of dopamine, .5 to 3 micrograms/kg/minute, was given. Two intravenous dopamine infusions (30 minutes each) were performed before and after the injection of metoclopramide (30 mg, intravenous bolus). Two washout periods were also included before and after metoclopramide administration. Dopamine induced a decrease of blood pressure from 171.9 + 6.35/103.6 +/- 3.12 to 152.7 +/- 7.55/93.8 +/- 2.97 mm Hg (P < .001) without altering heart rate, and it increased plasma insulin levels from 8.29 +/- .70 microU/mL to 12.09 +/- 1.83 microU/mL (P < .01). Metoclopramide caused no changes of blood pressure or plasma insulin levels. Hypotensive responses and plasma insulin increases due to dopamine were blocked by metoclopramide, however. The authors conclude that a dopaminergic receptor may be involved in some cardiovascular responses and in modulating insulin secretion in humans.

Effect of intravenous dopamine on blood pressure and plasma insulin in hypertensive patients.

Eleven patients with moderate to severe hypertension were pre-treated with oral labetalol 800-1200 mg/day for one week, prior to receiving two i.v. infusions of dopamine 1-3 micrograms/kg/min each of 30 min each, before and after the i.v. bolus injection of metoclopramide 30 mg. There were washout periods before and after the metoclopramide administration. Dopamine induced a significant decrease of blood pressure from 172/104 to 153/94 mm Hg without altering heart rate, and it increased the plasma insulin level from 8.3 to 12.1 microU.ml-1. Metoclopramide did not itself affect blood pressure or plasma insulin, but it did block the hypotensive response and rise in plasma insulin due to dopamine. We conclude that the pharmacological actions of intravenous dopamine on the cardiovascular system and on insulin secretion may be mediated by dopaminergic receptor stimulation.

Effects of prazosin and propranolol on blood lipids and lipoproteins in hypertensive patients.

Prazosin and propranolol were compared in an open, crossover study to determine their effects on plasma lipids and lipoproteins. After a four-week placebo period, 10 hypertensive patients were randomly assigned to prazosin treatment (Group I) and another 10 to propranolol treatment (Group II) for eight weeks. After a second four-week placebo period, treatment in each group was switched to the alternative drug for eight weeks. The mean blood pressure was reduced to normal levels (diastolic blood pressure less than or equal to 90 mm Hg) by both drugs--prazosin (1 to 8 mg per day) and propranolol (40 to 240 mg per day). The results of the study indicate that prazosin decreases serum cholesterol levels. In contrast, propranolol not only increases serum triglyceride levels and very-low-density lipoprotein cholesterol, but decreases total high-density lipoprotein cholesterol, high-density lipoprotein2 cholesterol, high-density lipoprotein2, and apoprotein A-I. The data suggest that propranolol may induce significant, potentially atherogenic changes in lipid metabolism, whereas prazosin may represent an advantageous alternative as an antihypertensive agent, especially in subjects with an already atherogenic lipoprotein profile.

Effects of prazosin and alphamethyldopa on blood lipids and lipoproteins in hypertensive patients.

The effects of prazosin and alphamethyldopa on blood lipids and lipoproteins were assessed in 20 patients with mild or moderate arterial hypertension. Parameters measured included serum cholesterol (CHO), triglycerides (TG), high density lipoprotein-cholesterol (HDL-CHO), insulin (I), glucose (G), and non-esterified fatty acids (NEFA). Prazosin -4 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.6/17.2 (systolic/diastolic pressure) mmHg. There was a significant decrease in CHO (-5.8%), in I (-16.5%), and in NEFA (-3.0%), and a significant increase in HDL-CHO (+15.5%). Alphamethyldopa 250-750 mg/day for 6 weeks in hydrochlorothiazide-treated patients lowered blood pressure by 18.8/14.6 (systolic/diastolic pressure) mmHg, accompanied by a non-significant decrease in CHO and TG, and significant increases in HDL-CHO (+10.3%), G (+8.5%) and NEFA (+6.4%). Thus, prazosin appears to have a more beneficial effect on blood lipids and lipoproteins than alphamethyldopa.

Systemic and cardiac haemodynamic interactions between guanfacine and hydrallazine in hypertensive patients.

The effect of guanfacine and hydrallazine on cardiovascular haemodynamics and on sympathetic nervous activity has been studied in 16 patients with essential hypertension. Two groups of patients were investigated: in Group A guanfacine brought the blood pressure back to normal (diastolic blood pressure less than or equal to 90 mmHg), and in Group B diastolic blood pressure was greater than 90 mmHg and required the addition of hydrallazine. Guanfacine significantly decreased heart rate, plasma renin activity and urinary excretion of noradrenaline, without altering cardiac contractility. In Group B, guanfacine 2 to 6 mg/day produced a significant decrease in blood pressure from 178.7/112.4 to 164.4/102.9 mmHg and in heart rate from 77.1 to 62.7 beats/min after 4 weeks of treatment. Guanfacine did not significantly alter preejection period, cardiac output or total peripheral resistance. Hydrallazine 50 to 300 mg/day caused a further reduction in blood pressure from 164.4/102.9 to 150.7/90.2 mmHg and an increase in heart rate from 62.7 to 72.1 beats/min. Limb blood flow was increased from 4.55 to 5.93 ml/100 g/min and limb vascular resistance was decreased from 39.55 to 23.6 mmHg 100 g X min/ml. Hydrallazine also caused a slight increase in plasma renin activity and urinary excretion of noradrenaline. It is concluded that guanfacine is a useful agent to block a hydrallazine-induced increase in sympathetic nervous activity.

Cardiovascular hemodynamic interactions between clonidine and minoxidil in hypertensive patients.

The systemic, cardiovascular hemodynamic and biochemical interactions between clonidine and minoxidil were studied in ten patients with refractory and/or accelerated hypertension. Clonidine in oral doses of 150 to 900 micrograms/day decreased mean blood pressure (MAP) 18.6 mm Hg (p less than 0.01), average heart rate (HR) 16.4 bpm (p less than 0.01), limb blood flow 1.63 ml/100 g min (p less than 0.05), plasma renin activity (PRA) 1.13 ng/ml/hr (p less than 0.025), and urinary noradrenaline excretion rate 16.45 micrograms/24hr (p less than 0.05). Clonidine increased the preejection period index (PEPI) 12.4 msec ( p less than 0.001), but did not alter cardiac index (CI), total peripheral resistance index (TPRI), limb vascular resistance nor dopamine beta-hydroxylase activity. When minoxidil in oral doses of 5 to 22.5 mg was added, a further decrease in MAP of 24.2 mm Hg (p less than 0.01) was observed; PEPI decreased 20.6 msec (p less than 0.01), limb blood flow decreased 13.2 mm Hg/min 100 g/ml (p less than 0.05), and total peripheral resistance index decreased 13.3 mm Hg/min m2/L (p less than 0.05). Minoxidil increased average heart rate 8.2 bpm (p less than 0.05), PRA 1.68 ng/ml/hr (p less than 0.05) and urinary noradrenaline excretion rate 5.0 micrograms/24 hr (p less than 0.01). Limb blood flow, cardiac index and dopamine beta hydroxylase activity were not significantly altered by minoxidil. Neither clonidine nor minoxidil affected cardiovascular responses to treadmill exercise. We concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.

Effect of indoramin and propranolol on cardiovascular response to cold in hypertensive patients.

Immersion of the hand into ice water (cold-pressor test) in nine hypertensive subjects induced elevation of mean blood pressure, increase of vascular resistance in the extremities, decrease of blood flow in the extremities, and increase in heart rate. The preejection phase of systole was not altered. Indoramin and propranolol, each alone and together, attenuated the pressor and other cardiovascular responses. Submaximal exercise increased heart rate during placebo treatment, a response only partially attenuated by indoramin, propranolol, and their combination, but it did not induce changes in mean blood pressure during any of the treatments.

Effect of prazosin on blood lipids and on thyroid function in hypertensive patients.

Nineteen patients with essential hypertension (EH) were studied as outpatients. After administration of chlorthalidone, 50 mg/day for 4 weeks, prazosin 1-4 mg/day (1.82 +/- 0.33 mg/day) was added for a period of 12 weeks. Prazosin lowered supine blood pressure from 149.7 +/- 2.85/102.0 +/- 2.75 mm Hg to 128.2 +/- 3.0/86.1 +/- 1.04 mm Hg (p less than 0.001). Prazosin did not alter heart rate significantly. Prazosin increased the thyroid stimulating hormone (TSH) from 3.63 +/- 0.33 microunits/ml to 4.83 +/- 0.45 microunits/ml (p less than 0.025), thyroxine (T4) from 10.03 +/- 0.29 micrograms/ml to 10.85 +/- 0.42 micrograms/ml (p less than 0.005), and decreased triiodothyronine (T3) from 36.65 +/- 0.62% to 35.42 +/- 0.56%, which was not significant. The free thyroxine index (FTI) increased slightly from 3.67 +/- 0.12 to 3.83 +/- 0.14 (p less than 0.025). However, all values remained within the normal range for the laboratory. Serum cholesterol increased insignificantly. Triglycerides decreased significantly from 223.4 +/- 50.6 mg/dl to 161.7 +/- 29.0 mg/dl (p less than 0.05). High density lipoproteins (HDL) increased significantly from 30.1 +/- 2.1% to 36.0 +/- 3.06 (p less than 0.025). Low density lipoproteins (LDL) decreased insignificantly and very low density lipoproteins (VLDL) decreased from 20.9 +/- 3.44 to 16.3 +/- 2.85 (p less than 0.005). The cholesterol ratio increased from 45.51 +/- 4.3 to 64.71 +/- 10.7 (+42.1%). These results indicate that, in patients with essential hypertension, prazosin is an effective antihypertensive agent and that it significantly increases HDL, decreases VLDL, and improves the cholesterol ratio.

Systemic and cardiac hemodynamic interactions between clonidine and minoxidil.

We examined the hemodynamic interaction between clonidine, a centrally acting antiadrenergic drug, and minoxidil, a potent antihypertensive vasodilator in 10 inpatients with refractory or accelerated hypertension or both. Clonidine in oral doses of 150 to 900 micrograms/day decreased average mean blood pressure 18.6 mm Hg (p less than 0.01), average heart rate 16.4 bpm (p less than 0.01), limb blood flow 1.63 ml/100 gm . min (p less than 0.05), and plasma renin activity 1.13 ng/ml . hr (p less than 0.025). It also increased the pre-ejection period index 12.4 msec (p less than 0.001), but did not alter the cardiac or total peripheral resistance indices. The addition of minoxidil in oral doses of 5 to 22.5 mg/day further decreased average mean blood pressure 24.2 mm Hg (p less than 0.01), preejection period index 20.6 msec (p less than 0.01), limb vascular resistance 13.2 mm Hg/min . 100 gm/ml (p less than 0.05), and total peripheral resistance 13.3 mm Hg/min . m2/l (p less than 0.01), pre-ejection period index 20.6 msec (p less than 0.01), limb vascular resistance 13.2 mm Hg/min . 100 gm/ml (p less than 0.05), and total peripheral resistance 13.3 mm Hg/min . m2/l concluded that clonidine can be used as an alternative to beta-adrenergic blockers to counteract the increased sympathetic nervous activity minoxidil induces.

Effect of minoxidil on sympathetic nervous activity in clonidine-treated hypertensive patients.

The effects of clonidine and minoxidil on sympathetic nervous activity has been studied in 10 patients with accelerated or resistant hypertension. Clonidine 150 to 900 micrograms/day caused a significant decrease in blood pressure of 18.6 mm Hg, of heart rate 16.4 beats/min, of plasma renin activity 1.13ng/ml h, and of urinary noradrenaline excretion 11.55 micrograms/day, and a significant lengthening of the pre-injection period of 12.4 ms. Minoxidil 5 to 22.5 micrograms/day caused a further significant decrease in blood pressure of 24.2 mm Hg, and significant increases in heart rate 8.2 beats/min, plasma renin activity 1.68 ng/ml h and of urinary noradrenaline excretion 5.0 micrograms/day, and a significant shortening of the pre-ejection period of 20.6 ms. Neither clonidine nor minoxidil altered plasma dopamine beta-hydroxylase activity or the cardiovascular responses to treadmill exercise. It is concluded that clonidine is a useful alternative agent to block a minoxidil-induced increase in sympathetic nervous activity.

Effect of propranolol on sympathetic nervous activity in hydrallazine-treated hypertensive patients.

1 The effect of propranolol was examined on a) blood pressure and heart rate responses due to i.v. hydrallazine b) modification of these cardiovascular parameters during cold pressor test c) urinary catecholamine excretion rate. 2 Intravenous hydrallazine reduced significantly mean blood pressure by 15.2 mm Hg and increased heart rate by 24.9 beats/min. Propranolol reduced significantly mean blood pressure by 19.0 mm Hg and heart rate by 14.1 beats/min. Hydrallazine plus propranolol caused a significant reduction of mean blood pressure (by 37.7 mm Hg) but this was not accompanied by a significant fall in heart rate (by 3.3 beats/min). 3 During the control period, cold pressor test increased mean blood pressure by 16.0 mm Hg. Heart rate was increased by 12.5 beats/min in four patients. However, there was a reduction in heart rate (5.5 beats/min) in two other patients. During the propranolol period, cold pressor test-induced increase of mean blood pressure was not reduced but propranolol blocked the increase of heart rate. 4 Urinary catecholamine excretion rate was increased during hydrallazine administration. This excretion was not modified by propranolol.