Effect Of Minoxidil Research Articles

Whole Body and Regional Hemodynamic Effects of Minoxidil in the Conscious Dog

Whole Body and Regional Hemodynamic Effects of Minoxidil in the Conscious Dog

Effect of Minoxidil on Cultured Keratinocytes

Minoxidil has been shown to stimulate hair growth and these studies were undertaken to determine whether the drug had a direct effect on keratinocytes. Cultures of human epidermal cells were treated with minoxidil and it was found that they survived longer than control cultures. In addition, minoxidil prolonged the time that cells could be passed after reaching confluence. The results suggest that minoxidil slows the senescence of keratinocytes, which is similar to what has been found with epidermal growth factor.

Side effects of minoxidil

Side effects of minoxidil

Serial electrocardiographic changes during long-term treatment of severe hypertension with minoxidil.

The effects of minoxidil on the electrocardiogram (EKG) were assessed in a prospective investigation of 112 patients with severe hypertension during an observation period representing 241.5 patient-years. Highly significant blood pressure reductions at rest and during exercise were achieved and maintained with the combination of minoxidil, beta-adrenergic blocking agents, and diuretics. In 90% of the patients, the initiation of minoxidil was associated with nonspecific T-wave changes in the EKG consisting of flattening or inversion, which ranged from slight to very marked. While these changes may initially appear disconcerting, the observations of this study show that they are not related to changes in heart rate or other clinical criteria associated with myocardial ischemia. The changes remain unaltered during the tachycardia of exercise, they are not influenced by beta-adrenergic blockage, and they generally revert to their control appearance during chronic treatment. During long-term treatment, a substantial reduction of the increased QRS voltages occurred.

Treatment of drug-resistant hypertension with minoxidil or angiotensin-converting enzyme inhibitor: blood pressure, renin, aldosterone, and electrolyte responses.

The effects of minoxidil and the angiotensin-converting enzyme inhibitor SQ 14,225 on blood pressure, sodium balance, plasma renin activity, plasma aldosterone concentration, aldosterone excretion rate, and renal function were studied in 11 drug-resistant hypertensive patients under controlled diets of sodium and potassium intake. Minoxidil treatment lowered blood pressure from 178/112 +/- 8/5 mm Hg (means +/- SEM) to 14/95 +/- 6/3 mm Hg. Plasma renin activity rose from 4.8 +/- 1.7 ng/ml/hr to 9.9 +/- 2.4; plasma aldosterone rose from 32.6 +/- 7.4 to 50.5 +/- 9.8 ng/dl; and aldosterone excretion rate rose from 7.6 +/- 1.3 to 15.2 +/- 3.5 micrograms/24 hr. Sodium retention could be controlled by increasing doses of diuretics, but a 10 mEq/day sodium intake in two patients resulted in significant increases of serum creatinine, and hyperkalemia was reversed by sodium loading. In five minoxidil-treated patients, substitution with the angiotensin-converting enzyme inhibitor SQ 14,225 lowered plasma and urinary aldosterone levels in two normal and high-renin patients but not significantly in three low-renin patients. Sodium excretion increased when aldosterone decreased, but blood pressure were more consistently controlled with minoxidil than with oral SQ 14,225.

Increased aldosterone metabolic clearance in hypertensive patients treated with minoxidil: an effect of greater hepatic perfusion.

Since minoxidil was previously shown to raise plasma renin activity (PRA) but not the plasma aldosterone concentration (PAC), the effect of minoxidil on the rate of aldosterone metabolic clearance was studied. After the addition of minoxidil to the antihypertensive regimen of 7 hypertensive patients, the aldosterone metabolic clearance rate increased from 1,110 +/- 91 to 1,570 +/- 180 liters/day (p less than 0.01), an overall increase of 41%. Hepatic blood flow, estimated from the clearance from plasma of indocyanine green, was increased in a group of minoxidil-treated patients compared to a comparable group not treated with minoxidil (p less than 0.01). Thus, although minoxidil induces an increase in PRA, PAC does not change, since aldosterone metabolic clearance increases. Minoxidil increased hepatic blood flow, and it was probably by this mechanism that the drug accelerated the rate of aldosterone clearance.

Long-term treatment with minoxidil in patients with severe renal failure.

Summary: Clinical trials have confirmed the effectiveness of minoxidil as an antihypertensive drug in patients with normal or mildly decreased renal function. In previous studies the number of patients with severe renal failure has been small or the duration of follow-up not long. We have treated 58 patients, most of them on maintenance hemodialysis, with minoxidil for refractory hypertension. In most patients treatment of hypertension was reduced to two drugs plus minoxidil, and blood pressure decreased significantly from 205/120 $ 10/5 to 150/80 $ 5/5 mm Hg (p

Clinical response of hypertensive children to long-term minoxidil therapy.

The long-term effects of minoxidil were evaluated in 11 hypertensive children (5 male, 6 female) who used minoxidil for a minimum of 6 months. The selection of these patients for minoxidil therapy was made on the basis that their systolic and diastolic blood pressures were greater than the 99th percentile for aged-matched normals, despite their use of at least three other antihypertensive drugs. The starting daily dose of minoxidil was between 0.1 and 0.2 mg/kg, administered in two divided doses (maximum, 5 mg/kg/24 hr). They also received propranolol and either hydrochlorothiazide or furosemide throughout the period of study. A significant reduction in blood pressure was noted 1 week after starting minoxidil. Although blood pressure continued to decrease during the following 2 weeks in association with an increase in minoxidil dosage, the levels of blood pressure recorded throughout the remainder of the period of evaluation did not differ significantly from the values at 1 week. All children developed hypertrichosis over the overhead, trunk, and extremities, regardless of drug dosage. This remitted in all cases within 3 months after minoxidil was discontinued. No other adverse reactions were observed.

ECG Changes During Long-term Minoxidil Therapy for Severe Hypertension

A prospective assessment of the effects of minoxidil on the ECG was carried out in a series of 80 patients with severe hypertension, representing an observation of 139.6 patient years. In combination with beta-adrenergic blocking agents and diuretics, minoxidil resulted in substantial reductions in blood pressure at rest and during exercise. Concomitant with the initiation of minoxidil treatment, ECG changes consisting of flattening or inversion of the T waves, ranging from slight to very marked, were observed in 90% of the patients. While these changes may be potentially disconcerting, the observations of this study show that they are not related to changes in heart rate or other clinical criteria associated with myocardial ischemia. They are not influenced by exercise or beta-blockade and they generally revert to control appearance during chronic treatment, at which time accompanying improvement in preexisting abnormalities of the T wave was frequently seen. During long-term treatment, a substantial reduction of increased QRS voltages was observed.

Effects of minoxidil on coronary collateral flow and acute myocardial injury following experimental coronary artery occlusion.

Although vasodilators may improve left ventricular function when left ventricular failure develops in patients with acute myocardial infarction, their effect on the coronary collateral circulation and on infarct size is not well established. Accordingly, the effects of minoxidil, a potent coronary and peripheral vasodilator, on collateral blood flow and ischaemic damage following coronary occlusion were studied. In open-chest anaesthetised dogs, two 20 min occlusions of the left anterior descending coronary artery were carried out. Acute myocardial injury, as reflected by epicardial S-T segment elevation and regional myocardial blood flow, measured by the radio-labelled microsphere technique, were determined during each occlusion. Minoxidil (1 mg·kg−1) was administered before the second occlusion and reduced mean arterial pressure from 15.7 ± 0.5 to 9.3± 0.4kPa (118± 4 to 70± 3 mmHg). Regional myocardial blood flow to the nonischaemic zone rose from 91 ± 7 to 225 ± 36 cm3·min−1·100−1, while flow to the border and centre of the ischaemic zone fell significantly (from 48 ± 2 to 15 ± 2 and from 33 ± 5 to 6± 2 cm3·min−1 ·100 g−1, respectively). At the same time, myocardial ischaemic injury increased: mean S-T segment elevation (S-T) and the number of sites exhibiting S-T segment elevation increased from 2.6 ± 0.5 to 5.2± 0.5 mV and from 4.1 ± 0.5 to 7.0 ± 0.5 sites, respectively. Thus, although minoxidil increased regional myocardial blood flow to the normal myocardium, it further decreased flow to the ischaemic area and intensified ischaemic damage. The reduction of collateral flow may result not only from a fall in perfusion pressure but also from the decrease in coronary resistance in the normal myocardium, leading to a redistribution of coronary blood flow.

Effects of minoxidil and nitroprusside on reflex increases in myocardial contractility.

1 The effects of nitroprusside and minoxidil on increases in myocardial contractility resulting from carotid artery occlusion were investigated in anaesthetized dogs. The results were compared with those produced by intravenous influsion of noradrenaline. 2 Nitroprusside and minoxidil attenuated the pressor responses produced by carotid artery occlusion. 3 Nitroprusside, but not minoxidil, attenuated the maximal myocardial contractility resulting from carotid occlusion. 4 The pressor and contractility responses to noradrenaline infusion were unaffected by either agent. 5 Nitroprusside failed to alter the myocardial responses produced by dimethylphenylpiperazinium. 6 These results, in conjunction with those of other investigators who have demonstrated that nitroprusside does not affect the release of noradrenaline from adrenergic neurons, suggest that nitroprusside may inhibit sympathetic nervous system reflex activity via an afferent and/or central component.

Management of severe childhood hypertension with minoxidil: A controlled clinical study

The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.

The effects of minoxidil on pulmonary and systemic hemodynamics in hypertensive man.

Pulmonary hypertension has been described as a possible complication of the antihypertensive vasodilator, minoxidil. A prospective study was undertaken in seven severely hypertensive patients refractory to multiple drug therapy. Treatment was initiated with fixed doses of hydrochlorothiazide (100 mg/day) and propranolol (160 mg/day) for a control period. Mean systemic arterial pressure, cardiac output, and pulmonary artery pressure were then compared before and after the addition of acute (5 day) and chronic (2 month) therapy with minoxidil. Mean arterial blood pressure decreased from a control value of 135 mm Hg to a value of 104 mm Hg acutely and 108 mm Hg chronically. Significant increases in mean cardiac output occurred with minoxidil therapy (from 4.2 L/min control to 5.4 L/min acutely and 5.1 L/min chronically) despite concomitant propranolol treatment. Mean pulmonary artery pressure did not increase either acutely or chronically. The data suggest that in patients with normal pulmonary hemodynamics prior to treatment, pulmonary hypertension does not develop during two months of minoxidil therapy.

Increased pulmonary vascular resistance with systemic hypertension: Effect of minoxidil and other antihypertensive agents

Recent case reports suggest that pulmonary hypertension could be caused by minoxidil, a new potent vasodilating antihypertensive drug. Therefore, we evaluated the incidence and severity of pulmonary hypertension in 110 patients with systemic hypertension. Fourteen patients were treated with minoxidil for 2 to 35 months (mean 19.9 months), 15 were treated with no drugs, and the remaining 81 patients received conventional antihypertensive agents of several types. Pulmonary vascular resistance correlated positively (P is less than 0.05) with systemic vascular resistance. Minoxidil-treated patients with hypertension previously refractory to conventional therapy had slightly lower pulmonary vascular resistance than other hypertensive subjects. There was no correlation between pulmonary vascular resistance and duration of minoxidil therapy or other types of antihypertensive regimens. The positive correlation between pulmonary and systemic vascular resistance suggests the possibility of a causal hypertension relation in the two vascular beds.

Effect of minoxidil on blood pressure and hemodynamics in severe hypertension

Eighteen patients with diastolic hypertension (100 to 120 mm Hg), in addition to propranolol, 160 mg daily, and hydrochlorothiazide, 100 mg daily, received progressively increased doses of either minoxidil or placebo in a double-blind crossover study. With minoxidil (average dose 19.7 mg) blood pressure decreased from 165/109 to 138/89 mm Hg without the appearance of orthostatic hypotension. Hypertrichosis and fluid retention did occur, with an average weight gain of 1.8 kg, concomitant with an increased plasma volume. Pulse rate and cardiac output increased; no significant changes were observed in plasma renin activity, renal plasma flow, glomerular filtration rate or excretion of catecholamines or aldosterone. Minoxidil appears to be a useful antihypertensive drug for treating patients who do not respond adequately to therapy with diuretic and beta adrenergic blocking agents.