Various Forms Of Hypertension Research Articles

Urinary kallikrein excretion and plasma DBH activity in hypertension.

Many factors are to be considered in maintaining normal blood pressure. Authors study the behavior of urinary kallikrein (U.K.) and plasma dopamine-beta-hydroxylase (DBH) activity in various forms of hypertension. The values of U.K. excretion in normals were 20.5 +/- 1.8 E.U./24 h. In essential hypertensive patients (9.4 +/- 2.0 E.U./24 h) U.K. decreased, while in secondary hypertension it was significantly higher (33.8 +/- 3.0 E.U./24 h). Plasma DBH activity in essential hypertensive patients (17.72 +/- 2.33 I.U./ml) was similar to controls (20.22 +/- 1.39 I.U./ml); in secondary hypertension the mean values of plasma DBH were decreased (12.31 +/- 2.55 I.U./ml). No correlation between U.K. and plasma DBH activity was observed in normals and in various forms of hypertensive patients. U.K. seems a more reliable factor than plasma DBH in defining the different types of hypertension.

Natriuretic response to saline infusion in normotensive and hypertensive man. The role of renin suppression in exaggerated natriuresis.

Previous studies have reported an exaggerated natriuresis in hypertensive man; however, a systematic appraisal of this response in various forms of hypertension has not been made. We measured fractional excretion of sodium (FENa) during a four hour intravenous infusion of 2 liters normal saline in 162 normal subjects and 120 hypertensives. Of these, 13 had primary aldosteronism (ALDO), 19 high renin (HRH), 30 low renin (LRH), and 57 normal renin (NRH) essential hypertension. FENa for normals (1.42%), NRH (1.57%), and HRH (1.46%) was similar. That for LRH (2.56%) and ALDO (4.18%) was elevated compared to the other three subgroups (P less than 0.001). Although the four hour FENa during saline infusion was associated with mean atrterial blood pressure (MABP) within the entire hypertensive population (r = 0.51), when the subgroups of the hypertensive patients were considered separately no association between FENa and MABP was identified. Moreover, the MABP of subjects with HRH was greater (P less than 0.05) than in those with NRH, although the FENa of the two subgroups was similar. Patients with ALDO and LRH have a greater natriuretic response to a salt load than do other subgroups of essential hypertension or normal subjects. The exaggerated natriuresis appears to be a feature of hypertension with renin suppression. The degree of exaggerated natriuresis in not solely a function of an elevated mean arterial blood pressure.

USE OF SARALASIN IN THE DIAGNOSTIC EVALUATION OF HYPERTENSION IN CHILDREN

Saralasin (S), a competetive antagonist of angiotensin II, has been used to evaluate renin-angiotensin dependent hypertension in adults. The purposes of this study were to determine 1) if S might be useful in the evaluation of hypertension in children and 2) if it would provide information about the involvement of the renin-angiotensin system in various forms of hypertension in the young. An IV infusion of S (0.4 to 0.8mg/min) was given to 21 children (4 to 18 years) with sustained hypertension (mean admission BP=162/114). All pats had complete diagnostic evaluation including renal arteriography. Pats were divided into 3 groups: hypertension secondary to renal parenchymal disease (RPH), reno-vascular hypertension (RVH) and essential hypertension (EH). The S test was considered to be positive when systolic BP decreased 10mmHg and diastolic BP decreased 6mmHg. A positive S test was obtained in 4 of 8 pats with RPH, 4 of 7 pats with RVH and 1 of 6 pats with EH. All pats with a positive S test had increased peripheral renin activity (PRA). Two pats with EH and 1 with RVH had increased PRA but negative S tests.. Four pats with RPH (3+ and 1-S test) and all 7 pats with RVH have had a surgical procedure to help control their hypertension. These results suggest that S may be useful in the diagnostic evaluation of hypertension in children. More experience and time are required to determine whether S can help predict surgical success for RVH and RPH in the young.

Effects of an analogue of angiotensin II, [Sar1,Ile8] ATII, on blood pressure, plasma renin activity and plasma aldosterone in various forms of hypertension

To investigate the effects of an analogue of angiotensin II (ATII), [Sar1, Ile8] ATII, on blood pressure, plasma renin activity (PRA), and plasma aldosterone (PA), the analogue was intravenously infused at a constant rate of 600 ng/kg/min for 30 minutes into 6 normal subjects and 37 untreated patients suffering from various forms of hypertension. Pressor responses with a peak at 5 to 10 minutes occurred in normal subjects and 18 essential hypertensive patients with low or normal PRA. Thirty minutes after infusion, a significant decrease in PRA with an increase in PA was observed with or without a significant increase in blood pressure in essential hypertensive patients with low or normal PRA as was also ob-served in normal subjects. On the other hand, in 8 essential hypertensive patients with high PRA, a patient with renal artery stenosis and high PRA and 3 patients with renovascular hypertension on a low sodium diet, the analogue induced a gradual decrease in blood pressure with an increase in PRA and a decrease in PA. In 2 hypertensive patients with high PRA, the analogue caused severe hypotension with bradycardia. In 4 patients with primary aldosteronism, a significant increase in blood pressure was observed without significant changes in either PRA or PA during the [Sar1, Ile8] ATII infusion.These results suggest that [Sar1, Ile8] ATII acts as a weak agonist under the normal or low secretion of renin, but as an antagonist under an excess of renin release in man, except for primary aldosteronism in which a discrepant agonistic action between vasculature and kidney or adrenal cortex was observed. From the activity of agonistic or antagonistic action of the ATII analogue, the usefulness of [Sar1, Ile8] ATII in making an etiological diagnosis of hypertension was discussed.

A vasopressor potentiator for norepinephrine in hypertensive rats.

Recently, attention has been given to a hyperresponsiveness to vasopressor agents in various forms of hypertension. Hypertrophy and/or “water-logging” of blood vessels associated with prolonged hypertension has been found to narrow vessel lu-mina and lead to such hyperresponsiveness (1). In addition, subnormal mono-amine oxidase activity accompanied by increased tissue norepinephrine concentration has been reported in genetically hypertensive turkeys, which also exhibited a greater vasopressor response to exoge-nously administered norepinephrine (2).Lately there has been a renewed interest in a “sensitizing factor” to catechol-amines in hypertension, but because of the diverse nature of some studies and the frequent utilization of inadequate controls, reports have been conflicting. Several investigators have found evidence for a vasopressor agent potentiating factor among hypertensive subjects (3-6), and a transmittable humoral factor has been suggested by a study that utilized the par-abiotic union of a ...

RENIN DEPENDENCY OF BLOOD-PRESSURE: Analysis by Angiotensin II Antagonist P113 in Hypertensive Patients Treated with Salt Depletion and Propranolol

The effect of infusion of the angiotensin II antagonist P113 on blood-pressure (B.P.) has been studied in 10 patients with various forms of hypertension under four different conditions: before and after salt depletion and with or without propranolol treatment. The fall in B.P. after P113 infusion significantly correlated with log P.R.A. (plasma-renin activity), irrespective of diagnosis or treatment. P113 infusion caused a consistent fall in B.P. only after sodium depletion. The changes in B.P. after P113 infusion and those induced by propranolol correlated only during sodium depletion, when P.R.A. values rose. It is concluded that sodium depletion induced "renin dependency" of B.P. in

Nephrology: An Annotated Bibliography of Recent Literature

Nephrology: An Annotated Bibliography of Recent Literature

Change in the renin dependency of blood pressure induced by volume depletion and/or propranolol therapy in hypertensive patients.

1. Plasma renin activity (PRA) and renin dependency of the blood pressure was analysed in ten patients with various forms of hypertension before and during treatment with volume depletion and/or propranolol. Renin dependency was tested by infusion of the specific competitive angiotensin II antagonist Sar1-Ala8-angiotensin II (P113). 2. The P113-induced fall of the blood pressure did correlate with the log PRA (r=0-888, P less than 0-001). This correlation was found irrespective of different types of hypertension and treatment schedules. 3. During volume depletion, PRA was stimulated and renin dependency of the blood pressure increased. Propranolol therapy suppressed PRA during normovolaemia as well as during volume depletion, and this was accompanied by a decrease of the renin dependency. 4. No incication was found that a given PRA is of special importance for blood pressure elevation in different patients. 5. Suppression of PRA by propranolol is one of the anti-hypertensive mechanisms of this drug.

Urinary kallikrein in dogs with constriction of one renal artery.

Urinary kallikrein is a renal enzyme that cleaves kininogen, an α-globulin substrate, to produce kallidin (lysyl-bradykinin), a potent vasodilator kinin (1). In the 40 years since kallikrein was first detected in human urine, a number of workers have shown that kallikrein excretion is altered in patients (2-5) and animals (6-8) with various forms of hypertension. We have shown that urinary kallikrein is subnormal in patients with essential hypertension and supranormal in patients with primary aldosteronism (4, 9, 10). We have also shown that urinary kallikrein is regulated by the activity of sodium-retaining steroids, and thus, by the level of sodium intake (11). The purpose of this study was to determine the effects of chronic renal arterial stenosis on kallikrein excretion in the dog.Methods. Nine female mongrel dogs weighing 20 to 25 kg were anesthetized with sodium thiamylol and halothane and then the left renal artery was narrowed by suture ligatures according to the method of Lupu and his co-workers...

Hemodynamic Concepts in Hypertension

By delineating the hemodynamic characteristics of various forms of hypertension, human and animal studies of cardiac output, vascular resistance, and blood viscosity in hypertensive disease are pointing the way toward more specific antihypertensive chemotherapy. Such studies provide a rational basis for the use of adrenergic-blocking and other drugs, singly or in combination, to achieve specific effects.

Antihypertensive action of propranolol: Specific antirenin responses in high and normal renin forms of essential, renal, renovascular and malignant hypertension

The antihypertensive effect of propranolol was evaluated in 96 patients with various forms of hypertension preclassified according to plasma renin activity considered in relation to urinary sodium excretion. In essential hypertension (no = 74) 74 percent of high-renin patients (14 of 19) exhibited striking blood pressure reductions and 66 percent of normal-renin patients (25 of 38) achieved diastolic pressures less than or equal to 95 mm Hg. In sharp contrast, propranolol was completely ineffective in 17 low-renin patients. In all 11 patients with unilateral renal artery or parenchymal disease propranolol also lowered blood pressure in proportion to control renin levels. The response was predictive of the antihypertensive benefit of surgery even in six “normal” renin patients. In eight patients with high-renin malignant hypertension, propranolol normalized renin, aldosterone and potassium levels and produced dramatic though often incomplete blood pressure correction. In one low-renin patient with the malignant syndrone propranolol was ineffective. Regardless of etiology, antihypertensive effectiveness of propranolol correlated with control renin levels and with the decrement in renin secretion. Thus, a simple biochemical measurement indexed against sodium excretion predicted antihypertensive drug responsiveness. These observations expose, for the first time, a role for renin in a major fraction of patients with essential hypertension. Renin-induced vasoconstriction appears to cause the hypertension in high renin and also in some normal renin patients in whom renin may be inappropriately high for sodium balance. The antihypertensive action of propranolol strikes at both vasoconstrictor and volume components of hypertension since inhibition of renin secretion naturally retards aldosterone secretion, thus preventing compensatory salt and water retention which often vitiates hypotensive therapy. Accordingly, propranolol added to either vasodilator or diuretic agents ought to improve hypotensive effect by curtailing reactive increases in renin and aldosterone: this should also reduce diuretic-induced potassium loss. Propranolol given alone may prove effective in a sizeable fraction of all hypertensive disorders and without inducing the dehydrated hyperreninemic state caused by diuretics. Therefore propranolol may prove to be an alternate first approach, except in lowrenin hypertensions where this type of therapy is ineffective and contraindicated.

Antihypertensive effect of spironolactone in essential, renal and mineralocorticoid hypertension.

1. The hypotensive effect of spironolactone has been studied in twenty-four patients with various forms of hypertension. 2. In essential hypertension a greater fall of blood pressure was achieved in patients with renin activity hyporesponsive to postural change than in those in whom renin responded normally to posture. 3. A poor hypotensive response was observed in patients with renal or renal arterial disease and secondary aldosteronism. 4. The variable hypotensive response seen in patients with primary aldosteronism predicted the response to adrenal surgery. 5. Blood pressure was not lowered by spironolactone in one case of 17-hydroxylation deficiency or in one case of malignant ovarian arrhenoblastoma producing aldosterone.

Studies on the Renin-angiotensin System in Younger Hypertensives

The renin-angiotensin system in various forms of hypertension in younger adults, refractory edema and normal controls was studied by measurement of serum renin, of serum angiotensinase and angiotensin infusion test. The attitudes of the renin-angiotensin system in renovascular hypertension, malignant hypertension and primary aldosteronism were significantly different from that in normal controls. The renin-angiotensin system in refractory edema without hypertension was similar to that in renovascular hypertension. In hypertension with unknown cause, subjects with hypertensive disposition showed increased pressor response to angiotensin infusion in spite of normal levels of serum renin. The studies on the renin-angiotensin system by these examinations are useful for differentiation of various forms of hypertension.

The natural history of hypertension

1. 1. Two hundred and twelve patients with various forms of hypertension were classified according to the changes in their optic fundi and the degree of target organ involvement. They were followed up for an average period of four years, the shortest follow-up interval being two years for any one patient. During the period of observation the patients received no antihypertensive drug therapy but were given more general medical treatment as indicated. 2. 2. Those with essential hypertension showed a strikingly different life expectancy, depending upon the presence or absence of sustained uremia. 3. 3. In the absence of sustained uremia, the degree of change in the optic fundi and the severity of other target organ involvement seemed most markedly to influence the patient's life expectancy. 4. 4. Those with elevated diastolic blood pressures, irrespective of the degree of elevation, who manifested benign changes in the optic fundi and no evidence of target organ decompensation enjoyed a life expectancy approximating that of the general population for a similar age group. 5. 5. In view of these findings and the fact that there is often marked lability in the diastolic blood pressures in patients in all stages of severity of essential hypertensive disease, evaluation of drug therapy should be based upon the degree of target organ involvement and optic fundal changes rather than upon the degree of elevation of the diastolic blood pressure.

Production of premature ventricular contractions by Rauwolfia.

Alkaloids of Rauwolfia serpentina (Ophioxylon serpentinum) are currently enjoying great popularity for treatment of a wide variety of disorders, ranging from insanity to various forms of hypertension. While this drug has been in use for many years in India, a large pharmacological literature is not available. Allen and co-workers, in discussing its use in hypertension, state that it inhibits sympathetic system and reduces blood pressure by direct action on hypothalamus. Apparent parasympathomimetic action. Produces tranquility without somnolence. Toxic symptoms are said to include nasal congestion and stuffiness, mild bradycardia, sedation, muscular aching and stiffness, laxation, and at times nightmares and mental depression. Paresthesias, twitching of the limbs, chattering of the teeth, and pruritus have also been reported. We wish to report an additional and possibly significant toxic effect—ventricular premature contractions. We have been unable to find any report suggesting cardiotoxic effects. In August, 1953, one of us (B. N. W.)

Pharmacodynamical tests in arterial hypertension and therapeutical applications

SummaryThe author describes the results of pharmaecodynamical tests which he applied in a series of cases of hypertension : S. C. injection of 1 mg of adrenalin, S. C. injection of 1 mg of atropin and oral administration of 7.5 mg of prostigmine Roche. He indicates the criteria he followed to establish a differential diagnosis between the various forms of hypertension. In essential hypertension the author has seen hypotension after atropin and prostigmine and hypertension after adrenalin in the great majority of cases. On the contrary, certain cases react with a hypotension to injections of S. C. and I. V. adrenalin.These cases also show other abnormal reactions to certain tests and the author examines the possibility of disorders of autonotic nervous system.In renal hypertension blood pressure increases after adrenalin. Administration of prostigmine or injection of atropin provokes hypotension whose intensity depends on the stage of evolution of the disease. Advanced cases don’t react at all.The author d...

THE ANTIDIURETIC HORMONE IN THE URINE IN EXPERIMENTAL AND CLINICAL HYPERTENSION1

Hypertension, experimentally induced in laboratory animals as well as the clinical form of this disorder, is accompanied by certain changes in salt and water metabolism (Grollman, 1947). These observations suggested the desirability of a study of the excretion of the antidiuretic principle in the urine in various forms of hypertension in order to determine to what extent the altered salt and water metabolism in hypertension is accompanied by changes in the antidiuretic activity of the urine. methods The procedures outlined in the preceding paper were utilized for the determination of the antidiuretic content of the urine. Twenty-four hour specimens of urine were collected from a group of patients suffering from hypertensive cardiovascular disease who had been followed in the hypertension clinic of the Parkland Hospital. Specimens were also collected from a series of rats and dogs in which chronic hypertension had been induced at least 6 months previously by the application of a figure-of-eight ligature to...