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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sodium depletion was induced in dogs to raise plasma renin activity (PRA) from 1.11 to 26.48 ng/ml/hr. Little overall change in blood pressure (BP) occurred, but cardiac output (CO) and central venous pressure fell, while total peripheral resistance and heart rate (HR) increased. A nonapeptide converting enzyme inhibitor (CEI) produced a fall in BP which was linearly related to log. PRA; the intercept with PRA was at 1.05 ng/ml/hr, close to the average value for dogs on a normal diet. The fall in BP with this agent was not accompanied by an increase in HR or CO. When Sar1-Ala8 angiotensin II was used to antagonize the action of angiotensin, the fall in BP was also linearly related to log. PRA. However, for a given level of PRA this fall in BP was less than that achieved with CEI and the intercept of BP fall with PRA was 2.6 ng/ml/hr. Again with this agent there was little change in HR or CO as BP was reduced. Thus, both antagonists lowered peripheral resistance without exciting the homeostatic reflexes indicating that, as PRA rose above the normal resting level, the angiotensin generated had both a direct and indirect effect in maintaining BP.
Hypertension
PMID:The role of angiotensin in the control of blood pressure during sodium depletion. 23 85

Previous studies have suggested that angiotensin II and sodium can act as alternative mechanisms in maintaining high blood pressure in chronic renovascular hypertension, In the present study, exchangeable sodium was measured in rats in which angiotensin II has been confirmed or excluded as the main cause of the hypertension. To determine the degree of participation of angiotensin II in the maintenance of the high blood pressure, we studied the mean blood pressure response to an angiotensin antagonist (1-Sar-8-Ala-angiotensin II) and to a converting enzyme inhibitor (SQ20,881). Rats with a decrease in blood pressure of less than 20 mm Hg, in response to both inhibitors, were classified as nonresponders; those with a decrease of 20 mm Hg or more, as responders. Fifty percent of the rats with two-kidney hypertension were nonresponders, and they had lower blood pressure and plasma renin activity than the responders. Further, these two-kidney, hypertensive, nonresponder rats had normal exchangeable sodium. The two-kidney hypertensive responders, on the other hand, had significantly higher exchangeable sodium than both the two-kidney, hypertensive nonresponders and the two-kidney control rats. These results suggest that angiotensin II and exchangeable sodium do not play a major role in the maintenance of the high blood pressure in the two-kidney hypertensive nonresponders. However, there appears to be an abnormal relationship between renin and exchangeable sodium in the two-kidney hypertensive responders that could contribute to the maintenance of the hypertension.
Hypertension
PMID:Exchangeable sodium in angiotensinogenic and nonangiotensinogenic renovascular hypertension. 23 88

The role of renin-angiotensin system has been examined in the maintenance of hypertension in acute and chronic two-kidney (36 weeks) and chronic one-kidney (12 weeks) Goldblatt hypertensive rats using three inhibitors of this system. The inhibitors used were URI-73A, a synthetic analog of lysophosphatidylethanolamine, which inhibits renin both in vivo and in vitro, SQ14,225, a potent converting enzyme inhibitor, and [Sar1, Thr8] angiotensin II, an angiotensin II antagonist. When the inhibitors were administered in acute (high renin) hypertensive rats, they all lowered blood pressure significantly. However, in the chronic (low renin) hypertensive phase, both renin and converting enzyme inhibitors lowered blood pressure, whereas, Sar1, Thr8 failed to lower blood pressure. The renin inhibitor lowered plasma renin activity (PRA), and SQ14,225 and [Sar1, Thr8] Ang II increased PRA. Further studies on water and electrolyte balance with one-kidney model hypertensive and uninephrectomized control rats showed no change in plasma volume. However, there was increased 24-hour urinary output and increased sodium excretion. This study indicates that in chronic renal hypertensive rats, blood pressure reduction is possible by either renin on converting enzyme inhibitor, but not by angiotensin antagonists. Since volume did not change either during the development or reversal of hypertension, volume did not appear to play a major role in the maintenance of hypertension.
Hypertension
PMID:Role of renin-angiotensin system in chronic renal hypertensive rats. 23 87

The short-term cardiovascular and endocrine effects of an orally active angiotensin converting enzyme inhibitor, SQ14,225, were evaluated in 17 subjects with drug-resistant hypertension (10 with essential and seven with renovascular hypertension). On normal dietary sodium, SQ14,225 (after 3 days at average dose of 664 mg/day) reduced mean arterial pressure (MAP) significantly (from 141 +/- 4 to 122 +/- 4 mm Hg, (SE), p less than 0.001). However, only eight of the patients achieved blood pressures within the normotensive range. Of eight patients with residual hypertension, seven exhibited further decreases in MAP (from 132 +/- 4 to 108 +/- 6 mm Hg (SE), p less than 0.001) when dietary sodium was reduced to 10 mEq/day. No rebound hypertension was noted when treatment was temporarily discontinued for 3 days in 11 patients. The reductions in blood pressure were not associated with either orthostatic hypotension or interference with baroreceptor reflexes. The values of supine plasma renin activity (PRA) were not always predictive of blood pressure responsiveness to the drug. With treatment, plasma aldosterone concentrations (PAC) decreased modestly (values from 40 +/- 9 to 22 +/- 3 ng/dl (SE), p less than 0.05). The plasma concentrations of cortisol, norepinephrine and serum potassium were left unchanged during the period of studies. The present study has not defined the exact mechanism by which SQ14,225 lowered blood pressure. Nevertheless, it indicates that this agent may be a practical therapeutic adjunct in the treatment of certain subsets of the human hypertensive population. The lack of serious interference with cardioscular and humoral homeostasis adds to its attractiveness as a therapeutic agent.
Hypertension
PMID:Converting enzyme inhibition with an orally active compound in hypertensive man. 23 90

Eight patients on chronic haemodialysis for six months to 7 years with hypertension resistant to ultrafiltration and antihypertensive therapy, received Captopril (SQ 14, 225) an orally active inhibitor of converting enzyme. With this therapy, blood pressure was controlled in the 4 patients with the highest plasma renin activity. In the other 4, this treatment had to be supplemented with "isovolumetric salt subtraction", i.e. following conventional dialysis, 1-2 litres of ultrafiltrate were replaced by an equal volume of 5% glucose. The slight hyponatraemia induced by this procedure (plasma sodium 128mmol/L) was well tolerated. This procedure allows the removal of an excess of body sodium and seems to be effective even when conventional ultrafiltration during dialysis has failed. Administration of Captopril either alone or combined with "isovolumetric salt subtraction" induced good control of blood pressure in all 8 patients.
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PMID:Captopril and salt subtraction to treat "uncontrollable" hypertension in haemodialysis patients. 23 15

To determine the relative importance of hormonal factors in mediating the hypotensive response to converting enzyme inhibition (CEI), plasma renin activity (PRA), angiotensin II, and bradykinin responses to SQ20,881 were measured in 20 supine patients with essential hypertension in balance on a 10 mEq sodium diet. Patients were divided into two groups according to their diastolic blood pressure response: responders had a decrement in diastolic pressure which exceeded 9 mm Hg, the upper value of the 95% confidence limits for normotensive patients studied under similar conditions; nonresponders did not. Compared to the nonresponders, responders not only had a higher control PRA (8.7 +/- 1.7 ng/ml/hr vs 4.8 +/- 2.1, p < 0.05) and larger decrement in plasma angiotensin II (18.7 +/- 4.9 pg/ml vs 3.2 +/- 1.7, p < 0.01), but also had a higher control bradykinin (3.2 +/- 0.7 ng/ml vs 1.1 +/- 0.2, p < 0.05) and larger increment in bradykinin (4.5 +/- 1.3 ng/ml vs 1.0 +/- 0.4, p < 0.05) following SQ20,881. Because SQ20,881 altered both angiotensin II and bradykinin concentrations, we assessed the contribution of blockade of angiotensin II formation by administering angiotensin II infusions to seven responders during coverting enzyme blockade, with the angiotensin II dose adjusted to restore diastolic pressure to control levels. The plasma angiotensin II level required to return blood pressure to control was 45 +/- 15 pg/ml higher than the control plasma angiotensin II level (p < 0.01), suggesting that some other factor(s), perhaps bradykinin, are also responsible for the hypotensive response to converting enzyme inhibition.
Hypertension
PMID:Converting enzyme inhibition in essential hypertension: the hypotensive response does not reflect only reduced angiotensin II formation. 23 66

One hundred fourteen hypertensives and 20 normal controls were examined using a new clinical technique of measuring 24-h urinary free 18-hydroxy-11-desoxycorticosterone (18-OH-DOC) excretion in response to dietary salt manipulations and ACTH injections. The object was to avoid potential errors of random plasma sampling. Mean urinary free 18-OH-DOC in normals on 110 milliequivalent sodium diet was 1.84 +/- 0.69 microgram (mean +/- SD) and represented about 2% of the daily secretion rate of this steroid. Both in normals and hypertensives, urinary free 18-OH-DOC approximately doubled on low salt (P less than 0.01 for each) and rose about 10 times in response to ACTH injection (P less than 0.05 and P less than 0.01, respectively). Plasma and urinary free 18-OH-DOC showed good correlation in patients with essential hypertension on a low salt diet (r = 0.45, P less than 0.01). Suppressed renin patients showed no propensity toward excess 18-OH-DOC excretion and hypertensives with elevated 18-OH-DOC could not be distinguished by their aldosterone levels, cortisol levels, nor their responses to various stimuli. These data suggest 18-OH-DOC is predominantly secreted under ACTH control and, to a smaller extent, in response to salt changes. Hypertension characterized by chronic overproduction of 18-OH-DOC forms only a small percentage of the hypertensive population. It is proposed that measuring 24-h urinary free 18-OH-DOC excretion may be the best method of assessing its rate of secretion without resorting to injection of radiolabeled material.
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PMID:Urinary free 18-hydroxy-11-desoxycorticosterone excretion in normal and hypertensive patients. 23 84

Information defining the renin-angiotension-aldosterone axis as a control system concurrently regulating salt balance and blood pressure has been applied to reexamine the role of renin in experimental and clinical forms of renovascular and renal hypertension, and thence to develop criteria for differentiating these entities. Experimentally, there are two models of renovascular hypertension; one is characterized by excess renin with reduced sodium (vasoconstrictor form) and the other by excess sodium with reduced renin (volume form). But with sodium depletion, the volume form converts to a vasoconstrictor form illustrating how the two factors coordinate to maintain blood pressure. In man, renovascular and renal hypertensions appear to be sustained by the same two mechanisms. Studies in man show that, in the absence of unilateral disease, the supine renal venous renin level in each kidney is consistently 24 percent higher than the peripheral level. Because of this constant relationship, the peripheral renin level is a measure of the renal secretion rate. Our studies indicate the curable unilateral renovascular hypertension is, in fact, renin-dependent vasoconstrictor hypertension. Three criteria, derived from four renin measurements, identify this situation: (1) Hypersecretion of renin is reflected by a high peripheral level when indexed against sodium excretion. (2) Lateralization of renin secretion with contralateral suppression rules out occult bilateral disease. It is indicated by V-A equal 0 from the uninvolved kidney. (3) (V-A)/A greater than 48 per cent from the ipsilateral kidney supports unilateralization. With data derived from patients with essential hypertension as a reference, the degree to which (V-A)/A is greater than 0.48 can be used to estimate the degree of renal ischemia, using Fick's principle. Corroborative evidence to support these three criteria can be developed from the blood pressure response to angiotensin blocking drugs or to antirenin therapy with propranolol. Clinical analysis validates these criteria to identify curable hypertension from unilateral renovascular or parenchymal disease. In patients with either occult or overt bilateral renal disease, the volume factor often predominates and is expressed by some suppression of plasma renin levels. Continued
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PMID:The renin axis and vasoconstriction volume analysis for understanding and treating renovascular and renal hypertension. 23 77

The evolution of malignant hypertension was studied under metabolic balance conditions in 11 uninephrectomized rats given deoxycorticosterone acetate and 1% NaCl as drinking water. Changes in sodium and potassium balance were related to changes in blood pressure, plasma renin activity, hematocrit, and kidney histology. After 3-4 weeks of steadily positive sodium balance accompanied by continuously increasing blood pressure up to 185 plus or minus 19 (SE) mm Hg, periods of sodium loss accompanied by evidence of hemoconcentration were observed marking the onset of the malignant phase as defined by the development of fibrinoid necrosis in the kidney. Plasma renin activity remained markedly suppressed both at the fourth week (0.33 plus or minus 0.02 ng/ml hour-1) when the sodium balance was positive and the kidney biopsy negative and at the end of the experiment (0.35 plus or minus 0.36 ng/ml hour-1) when the sodium balance was negative and the kidney histology revealed malignant vasculitis. Infusion of the angiotensin II inhibitor 1-Sar-8-Ala-angiotensin II consistently failed to affect blood pressure, and the kidney tissue norepinephrine level was reduced (0.054 plus or minus 0.01 mug/g) compared with the control level (0.132 plus or minus 0.02 mug/g). We conclude that malignant vasculitis in this model is preceded by hypertension associated with sodium and water retention and is accompanied by negative sodium balance, decreases in body weight, falling blood pressure, and hemoconcentration without demonstrable participation of the renin-angiotensin system or the renal catecholamines.
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PMID:Malignant hypertension resulting from deoxycorticosterone acetate and salt excess: role of renin and sodium in vascular changes. 23 7

Adequate treatment of hypertension requires that the physician understand the pharmacologic actions of antihypertensive agents. Although no drug is without adverse reactions, it should be possible to choose an agent or combination of agents which can effectively lower blood pressure and be tolerated by the patient. The indications, proposed mechanisms of actions and adverse effects of the following antihypertensive drugs are discussed: thiazide diuretics, spironolactone, triamterene, trimethaphan, Rauwolfia alkaloids. guanethidine, bethanidine, methyldopa, clonidine, pargyline, propranolol, hydrazaline, minoxidil, guancydine, diazoxide and sodium nitroprusside.
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PMID:Current therapy of hypertension. A pharmacologic approach. 23 41


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