Kwan Eun Kim

Hemodynamics of Hypertension in Chronic End-Stage Renal Disease

This study was undertaken to define the hemodynamic changes in hypertension of chronic end-stage renal disease. Mean cardiac index in 75 uremic patients was higher (P < 0.001) than that of 42 normal volunteers while stroke index was not different from normals. The higher cardiac indices of uremic patients were accounted for by increased heart rates. Despite the significantly higher blood pressure in the uremics, their mean total peripheral resistance index was not different from that of normals.The total group of 75 patients included 52 hypertensive and 23 normotensive uremics. Cardiac index, heart rate, and stroke index were the same in 52 hypertensive and 23 normotensive uremics while mean total peripheral resistance index of hypertensive uremics was higher (P < 0.001) than normotensive uremics. Therefore, the hypertension in end-stage renal disease is sustained by a high total peripheral resistance.Bilateral nephrectomy in 12 hypertensive uremics resulted in no changes in cardiac index; a consistent decrease in blood pressure (P < 0.001) and a decrease in total peripheral resistance index (P < 0.001) occurred. Bilateral nephrectomy in eight additional uremics with malignant hypertension resulted in an actual increase in cardiac index (P < 0.001) with a consistent reduction in blood pressures (P < 0.001) and an even more dramatic decrease in total peripheral resistance (P < 0.001).These findings imply that a vasopressor substance of renal origin increasing peripheral resistance is the major factor in the pathophysiology of renal hypertension in the late stage of its natural history.

Clonidine: A new antihypertensive agent

Abstract Intravenous administration of clonidine in hypertensive patients resulted in a short, hypertensive response followed by a prolonged reduction of both systolic and diastolic pressure. The antihypertensive response was associated with a decrease of total forearm blood flow, while the muscle blood flow of the calf was unchanged or moderately increased. Skin blood flow showed a sharp reduction initially, followed by a slow return to control levels. In patients with essential hypertension the reduction in blood pressure after acute oral administration of clonidine was associated with a decrease in cardiac output in the supine position. In contrast, in the upright position, a reduction in both cardiac output and total peripheral resistance were observed. During the antihypertensive response, renal blood flow and glomerular filtration rate were maintained, both acutely and chronically. Intravenous or intramuscular administration of clonidine proved to be very effective in hypertensive emergencies. In 174 hospitalized patients, prolonged oral administration resulted in significant improvement of the blood pressure in 61 percent of the cases. In 115 ambulatory patients, significant improvement occurred in 64 percent. Clonidine was added to the therapeutic regimen of 20 ambulatory patients who had remained hypertensive during diuretic therapy alone, and 16 (80 percent) of the 20 showed a significant antihypertensive response in both the supine and upright positions. The most common side effects were drowsiness and dryness of the mouth. Because of its marked efficacy and the beneficial cardiovascular and renal effects, clonidine represents a most useful addition to our antihypertensive armamentarium.

Ethacrynic acid and furosemide: Diuretic and hemodynamic effects and clinical uses☆

Abstract Ethacrynic acid and furosemide are the most potent diuretic agents currently available. Although the evidence for a proximal tubular site of action is conflicting, the main action of both agents is inhibition of sodium reabsorption along the ascending loop of Henle. Acute administration of ethacrynic acid and furosemide may produce a transient slight increase in both glomerular filtration rate and renal plasma flow, which is followed by a decrease in glomerular filtration rate and renal plasma flow with diuresis and dehydration. In patients who do not have congestive heart failure, acute administration of either drug results in a decrease in plasma volume, central venous pressure and cardiac index, and an increase in arteriovenous oxygen differences. In patients with severe congestive heart failure, plasma volume and central venous pressure fall, but cardiac index increases and arteriovenous oxygen difference narrows. Both drugs have rapid and short duration of diuretic action and wide and steep dose-response curves. Therefore, both drugs can be used in patients with mild to severe congestive heart failure or fluid retention. Both drugs are also effective despite the presence of hypoalbuminemia, acid-base and electrolyte imbalance and a low glomerular filtration rate. Therefore, refractoriness to either agent is unusual in the absence of severe renal failure. Neither drug has been widely used for antihypertensive therapy. No marked difference in antihypertensive potency from that of standard thiazide drugs has been noted. Both drugs are especially useful in those patients with severe hypertension who have concomitant renal failure or congestive heart failure. In this group of patients they help to maintain adequate urinary output and potentiate other antihypertensive drugs. Despite the potent diuretic action of both drugs, side effects are relatively infrequent. However, close monitoring of diuretic response, and acid-base and electrolyte status is recommended.

Effect of chronic administration of propranolol on the blood pressure and heart weight in experimental renal hypertension

Abstract Chronic administration of propranolol did not alter the course of severe renal hypertension in the rat. Twenty and forty days after the induction of hypertension, blood pressure, ventricular weight and plasma renin concentration were determined. On day forty, at equivalent levels of blood pressure, the ventricular and the ventricular/body weight ratio was significantly lower in the propranolol treated group (18.6%; 22.9%). It is suggested that propranolol may mitigate the cardiac hypertrophy associated with hypertension. This effect is independent of the blood pressure.

Studies on the natriuretic effect and site of action of indapamide

SummaryA double-blind, placebo-controlled study was carried out in 42 normal male volunteers to determine the natriuretic effect of indapamide in increasing doses. After α 3-day period of dietary stabilization on relatively high sodium intake and unlimited water intake, groups of 6 subjects were given single doses of placebo or 0.5 mg, 1.0 mg, 2.5 mg, 5 mg, 10 mg, 20 mg, or 30 mg indapamide. Urinary volume and electrolyte excretion were measured for the periods 0 to 4 hours, 4 to 8 hours, and 8 to 24 hours after drug administration. No natriuretic effect was evident with 0.5 mg indapamide. With doses of 2.5 mg and 5 mg, there was a significant progressive increase in sodium excretion but not of potassium. Doses of 10 mg and 20 mg continued to show this pattern but the natriuretic effect was not greater on a 24-hour basis than with the 5 mg dose. No further increase in natriuresis was observed with 30 mg indapamide, but there was a significant kaliuresis and a marked increase in urinary volume.In a study i...

The antihypertensive effect of indapamide in low doses

SummaryA dose-titration study was performed to assess the minimal antihypertensive dose of indapamide and the dose-response curve in ambulatory patients with mild essential hypertension (diastolic blood pressure 90 to 114 mmHg). After a 30-day placebo period, patients received 0.5 mg indapamide daily for 6 weeks and this was increased to 1.0 mg daily for a further 6 weeks in those not responding, i.e. with a standing diastolic pressure greater than 90 mmHg. Although indapamide demonstrated an antihypertensive effect at these dose levels, normalization of blood pressure was achieved in only 2 of the 13 patients on 0.5 mg per day and in none of the 11 patients receiving 1.0 mg per day. No clinical side-effects or abnormalities in serum potassium and uric acid were noted.

Role of adrenergic innervation in experimental renal hypertension.

Abstract Renal hypertension was induced by ligation of the aorta between renal arteries in rats sympathectomized with 6-hydroxydopamine. In the early phase, equally severe hypertension developed in the denervated group as compared to innervated controls. Later, blood pressure was lower in the denervated rats. Initially, increases in plasma renin were seen in both groups; the levels, however, were markedly lower in the denervated rats. Later, the renin levels were similar and not different from baseline. It is concluded that adrenergic neural activity is not essential in the development of renal hypertension; the maintenance of the chronic state, however, depends in part on adrenergic innervation.

Clonidine, a New Potent Antihypertensive Agent.

Excerpt Clonidine (Catapres⌖) is a new imidazoline derivative with potent antihypertensive effect. The acute hemodynamic effects of Clonidine were evaluated in seven hypertensive patients. Two dist...

Measurement of Intra-Arterial Blood Pressure and Cardiac Output through the Bovine Artegraft

Serial hemodynamic studies have become increasingly important in hypertension research. These studies have been accomplished using the A-V shunt. The progressive decline in the number of A-V shunts in favor of the A-V fistula has limited the number of measure cardiac output, the intra-arterial blood pressure cannot be measured through it. The present paper describes a technique for measuring both the cardiac output and direct intra-arterial blood pressure using the bovine artegraft.

Evidence for the Renal Origin of the Malignant Phase of Essential Hypertension.

Excerpt Six uremic patients with malignant phase of essential hypertension were studied before and after bilateral nephrectomy. All patients had documented essential hypertension for 2 to 10 years....