Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.11.18 (MAP)
 7,412 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sixteen patients (11 M, 5 F), median age 41 years, with essential hypertension insufficiently controlled on hydrochlorothiazide 75 mg/day (DBP greater than or equal to 100 mmHg) were investigated. Plasma renin concentration (PRC), angiotensin II concentration (PA II), aldosterone concentration (PAC), plasma noradrenaline concentration (PNAC), plasma volume (PV) and exchangeable sodium (NaE) were determined and a saralasin-infusion (5.4 nmol/kg/min) was carried out while the patients were on thiazide alone, and in fourteen cases, repeated 3 months later after addition of a beta-blocker (propranolol 6, metoprolol 6 and atenolol 2 patients). On thiazide alone PRC, PA II and PAC was higher than normal in the group as a whole and the angiotensin II-inhibitor, saralasin, caused a significant decrease in MAP in twelve out of sixteen patients. After addition of a beta-blocker SBP and DBP decreased from 164/109 mmHg to 136/94 mmHg. PRC and PA II decreased by 40% and 58%, respectively. At this point saralasin caused no significant change in MAP. No close correlation was found between changes in BP on beta-blocker treatment and either PRC, PA II or saralasin response on thiazide treatment. PV, NaE, PAC and PNAC did not change sigificantly. It is concluded that in pts with thiazide-induced stimulation of the renin-angiotensin system (RAS) addition of a beta-blocker leads to suppression of RAS and the angiotensin II dependence of the blood pressure is nearly abolished. This mechanism might well contribute to the antihypertensive effect of beta-blockade in this particular situation. However, the pharmacological changes induced by beta-blockade are very complex, and most likely other factors are involved in the antihypertensive effect of beta-blocking drugs.
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PMID:Angiotensin II blockade during combined thiazide-beta-blocker treatment. 610 82

The effect of saralasin infusion on systemic hemodynamics, plasma renin activity (PRA), and aldosterone levels was studied under various conditions of sodium balance in 25 patients with essential hypertension. The results of 66 paired observations were statistically analyzed, to elucidate some controversial aspects of the mechanisms of saralasin action. The total peripheral resistance index (TPRI) increased when saralasin had an agonistic effect on blood pressure (BP) and decreased when it acted as an antagonist. The TPRI changed more than the BP by an inversely directed change in the cardiac index (CI). In addition, the changes in the CI were only weakly correlated with the changes in MAP; CI decreased consistently when BP increased but showed no distinct pattern when saralasin acted as an antagonist. The pulse rate did not change under any of the conditions applied. The present findings suggest that in addition to its antagonistic effects on peripheral circulation, saralasin has some action on the heart and autonomic nervous system. The observed changes in the plasma aldosterone level were in accordance with the changes in TPRI and did not point to a difference between adrenal and vascular sensitivity to saralasin or angiotensin II. The overall hemodynamic responses were related to the existing level of PRA. No correlation was found between the degree of volume depletion and the blood pressure response during saralasin after elimination of the effect of PRA by partial regression analysis. These findings do not support the concept that more information about the renin dependency of the BP is provided by the BP reaction to saralasin than by determination of the PRA.
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PMID:Systemic hemodynamic and hormonal responses during angiotensin II blockade with saralasin. 616 55

Twenty-two patients, aged 33-72 years, with uncomplicated essential hypertension were given sequential incremental intravenous infusions of sodium nitroprusside, each of 10 min duration, to examine the determinants of the vasodepressor response. Changes in mean arterial pressure (delta MAP), heart rate (delta HR), and plasma norepinephrine (delta nc) were determined at the end of each infusion period. The slopes of the dose-response curves obtained were directly proportional to predrug blood pressure (p less than 0.0001) and inversely proportional to baroreflex sensitivity as measured by the slope of the delta HR vs. delta MAP relationship (p = 0.0007). Baroreflex sensitivity was in turn inversely proportional to, and approximately equally dependent on, predrug blood pressure and age (p = 0.0116). Thus, the slopes of the dose-response curves were determined by both predrug blood pressure and patient age. The relationship was such that predrug blood pressure accounted for approximately 75% of the variability in the slope of the dose-response curve, and age for only 25%. This suggests that the age-related reduction in baroreflex sensitivity is mechanistically different from the hypertension-related reduction and is of less importance in modifying homeostatic responses to vasodilation.
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PMID:Age and blood pressure determine vasodepressor response to sodium nitroprusside. 620 85

Factors contributing to the blood pressure (BP) response to changes in dietary sodium intake were studied in 25 patients with essential hypertension (EH). Relevant clinical, biochemical and haemodynamic variables were measured after two weeks on a low sodium diet (LS, 50 mmol) and after two weeks on a high sodium diet (HS, 300 mmol). BP was significantly higher during HS. The difference in mean arterial pressure between HS and LS (delta MAP) was taken as a measure of sodium sensitivity. delta MAP was directly related to age, initial BP, plasma noradrenaline during HS and changes in forearm vascular resistance. It was indirectly related to plasma aldosterone during LS. No correlation was found with renin or with the excretion of urinary kallikrein. It is concluded that sodium sensitivity in EH is related to age and blood pressure and is predominantly mediated by changes in vascular resistance to which aldosterone and adrenergic mechanisms are likely to contribute.
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PMID:Clinical biochemical and haemodynamic correlates of sodium sensitivity in essential hypertension. 640 Jan 14

In 25 outpatients with essential hypertension, sodium sensitivity, defined as the difference in mean arterial pressure (delta MAP) between 2 weeks of high-sodium (300 mmol per day) and 2 weeks of low-sodium (LS) intake (50-100 mmol per day), was studied in relation to the plasma norepinephrine (NE) level, NE release, and pressor response to intravenous NE. In addition, forearm blood flow (FBF) was measured by plethysmography. There were two control periods of regular sodium intake, one of 4 weeks' duration at the beginning of the study and one of 2 weeks' duration at the end. The delta MAP ranged from +18 to -8 mm Hg. The eight patients in whom delta MAP was greater than 10 mm Hg were regarded as salt-sensitive. When compared with salt-insensitive subjects, salt-sensitive patients had higher plasma NE levels in the control period (p less than 0.05) and after 2 weeks of HS intake (p less than 0.01). Sodium sensitivity was directly related to the change in plasma NE between the HS and LS periods (p less than 0.001). The NE release decreased in salt-insensitive subjects whereas it increased in salt-sensitive patients between the LS and HS periods. Changes in NE release were directly related to sodium sensitivity (p less than 0.05). The pressor response to NE was not significantly influenced by changes in sodium intake. The FBF fell in salt-sensitive patients and increased in salt-insensitive subjects between the LS and HS periods. Sodium sensitivity was directly related to the change in forearm vascular resistance (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Adrenergic activity and peripheral hemodynamics in relation to sodium sensitivity in patients with essential hypertension. 651 41

Regulation of aldosterone secretion by sodium chloride is impaired in a group of essential hypertensives: high-salt diet fails to suppress aldosterone in these patients despite low renin values. The mechanism of this impaired regulation of aldosterone has not been clarified so far. We tested the sensitivity of aldosterone secretion and blood pressure to A II in 20 normotensive controls (aged 20-60, MAP 92 +/- 3 mm Hg), in ten normotensives with one or two parents with hypertension, and in 21 patients with essential hypertension (aged 17-65, MAP 119 +/- 4 mm Hg). After a period of 6 days on high-salt intake (300-320 mEq Na+/day), A II (0.1, 0.5, 1.0 and 2.0 ng/kg/min) was infused, each concentration for 30 min. According to aldosterone excretion during sodium loading, patients were divided into group A with complete suppression (n = 12, aldosterone excretion 3.6 +/- 0.4 microgram/day) and in group B with insufficient suppression (n = 9, aldosterone excretion 15.5 +/- 2.3 micrograms/day). Despite similarly low plasma renins, rise of serum aldosterone levels during A II infusion was significantly higher in group B patients than in group A patients and normotensive controls. Rise in mean arterial blood pressure, however, brought about by graded A II infusion was similar in both groups of hypertensives and in normotensive controls. The results demonstrate an increased adrenal sensitivity to A II in a subgroup of essential hypertensives only. A similar adrenal hypersensitivity to A II found by others in patients with hyperaldosteronism due to adrenal hyperplasia supports the hypothesis that the same mechanism underlies both disorders.
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PMID:Cardiovascular and adrenal sensitivity to angiotensin II in essential hypertension. 652 58

In order to determine factors contributing to sodium induced changes of blood pressure, 20 patients with essential hypertension were studied when on their regular sodium intake and after two weeks of a low sodium diet (50 mmol daily) and two weeks of a high sodium diet (300 mmol daily). There were two periods of regular sodium intake, one of four weeks at the beginning and one of two weeks at the end of the study. The change in mean arterial pressure between the high and low salt diets (delta MAP) was regarded as a measure of sodium sensitivity, and was directly correlated with age and initial blood pressure. Compared with non-responders, responders (delta MAP 10 mmHg or more) showed a lesser activation of the renin-angiotensin-aldosterone system during the low salt period. The response to the administration of intravenous frusemide was not helpful in predicting sodium sensitivity. A significant but relatively small (4.2 mmHg) reduction in MAP was obtained during low salt period compared with the first period of regular sodium intake. The data suggest that moderate dietary sodium restriction can help to reduce the blood pressure of the relatively older patient with hypertension.
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PMID:Sodium sensitivity in essential hypertension: role of the renin-angiotensin-aldosterone system and predictive value of an intravenous frusemide test. 653 May 38

From a hemodynamic point of view, an adequate response to antihypertensive therapy would be restoration of a normal circulatory system. In most patients with mild to moderate essential hypertension considered to need drug therapy, the cardinal hemodynamic disturbance is an increased total peripheral resistance (TPR) and a normal or reduced cardiac output (CO). During a 10- to 17-year follow-up of untreated hypertensives, a gradual increase in TPR, increase in MAP, and a decrease in CO and stroke volume (SV) were seen. Hemodynamic responses to chronic drug therapy were studied at rest and during exercise in 250 men with mild to moderate essential hypertension in WHO Stage I. A significant reduction in TPR was seen on thiazide diuretics, nifedipine and verapamil, but there was no increase of subnormal CO or SV. A greater normalization of central hemodynamics was achieved by prazosin, which induced a reduction in TPR and an increase in CO and SV, particularly during exercise. In contrast, beta-blocker therapy was associated with a chronic reduction in CO and heart rate (HR) and usually no reduction in TPRI below pretreatment values. The chronic CO reduction was associated with an increase in arteriovenous oxygen difference. In 14 patients with therapy-resistant hypertension, a marked increase in TPR was found. Captopril induced a reduction in TPR with rest and exercise, and also a reduction in cardiac output. Prolonged therapy for 5 years with beta-blockers did maintain blood pressure control, but with no further decrease in TPR.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Hemodynamic response: decrease in cardiac output vs reduction in vascular resistance. 662 61

Baroreflex activity is a determinant of the homeostatic response to alteration in blood pressure. We examined the factors that determine the magnitude of the vasodepressor response to sequential incremental intravenous infusions of sodium nitroprusside (NP), 0.05 to 6.4 micrograms/kg/min, in eight male patients with essential hypertension. Each infusion level was of 10 minutes' duration. Change from control values of mean arterial pressure (delta MAP), heart rate (delta HR) and plasma norepinephrine (delta NE) were obtained at the end of each infusion level. Significant correlations were found between delta MAP vs log dose NP, delta HR vs delta MAP and delta NE vs delta MAP for each patient (p less than 0.05). However, the slopes of these relationships varied widely between subjects and were significantly correlated with the control blood pressure of each patient. In addition, the sympathetic responsiveness, as measured by delta NE vs delta MAP, was inversely correlated with the degree of vasodepressor response seen. Thus, the magnitude of the vasodepressor response was determined by two major factors: 1) the predrug blood pressure, possibly reflecting altered vascular geometry with hypertension; 2) the degree of sympathetic response, which probably acts by mediating the degree of reflex alpha-adrenergic-mediated arteriolar vasoconstriction.
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PMID:Baroreflex sensitivity modulates vasodepressor response to nitroprusside. 684 71

In a prospective, double-blind, intraindividual, cross-over, placebo-controlled multicenter study, clinical and biochemical effects of once daily postprandial dose regimens of 50, 100, and 200 mg spironolactone were investigated in 45 outpatients with primary hypertension, WHO (World Health Organization) Stage I-II. Each of the three active therapy periods, which were randomly allocated to patients, were of 2 months' duration, with intervening placebo periods, Clinical and biochemical parameters, including furosemide-stimulated plasma renin activity (PRA), were recorded at regular intervals. All three spironolactone doses resulted in statistically significant blood pressure (BP) reductions independent of initial pretreatment levels and yielded satisfactory BP control in more than half of the patients. The 200 mg daily dose of spironolactone was found to be more effective than 50 but not 100 mg. When, correlating blood pressure response (delta MAP) to PRA, the profiling for positive spironolactone responders was characterized by high age and low PRA, irrespective of sex. Spironolactone therapy resulted in decreased serum sodium and magnesium values; potassium, creatinine, urate, and triglyceride levels were increased. However, all treatment values were within normal ranges. Side effects were infrequent and mainly of endocrine nature.
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PMID:Clinical and biochemical effects of spironolactone administered once daily in primary hypertension. Multicenter Sweden study. 699 72


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