Resting Plasma Renin Activity Research Articles

Hemodynamic and neurohumoral profile in patients with different types of hypertension in pregnancy

Hypertension in pregnancy is a frequent disorder that includes a spectrum of conditions. We aimed at comparatively evaluating the hemodynamic, echocardiographic and biohumoral profile of a sample of pregnant Caucasian women with different form of pregnancy-related hypertension. We enrolled 39 non-hypertensive pregnant women (NP), 26 with Chronic HBP in pregnancy (CH), 24 with gestational hypertension (G-PIH), and 33 with pre-eclampsia. We recorded and compared blood pressure (BP), echocardiographic parameters, resting plasma renin activity (PRA) and plasma aldosterone (PA), Plasma levels of atrial (ANP) and brain natriuretic peptide (BNP). PE patients had a significantly higher BP than either G-PIH or NP patients. PE patients had also significantly lower cardiac output than NP, G-PIH and CH. In comparison to NP patients, the total peripheral vascular resistance was 61% higher in PE women and 38% higher in CH patients. All echographic parameters were significantly more altered in PE patients when compared with NP, in respect to any other form of hypertension. Either ANP (+35%) and BNP (+40%) were significantly higher in PE patients than in controls. The PRA was reduced in PE and CH patients when compared either with NP (-38 and -35%, respectively) or G-PIH (-47 and -43%, respectively). On the basis of our data, we can conclude that PE is the gestation associated hypertension with the largest anatomical, functional and biohumoral involvement, and so it has to be involved in a more intensive monitoring and evaluation.

Response to angiotensin inhibition in rats with sustained renovascular hypertension correlates with response to removing renal artery stenosis

Purpose: Sustained (late-phase) renovascular hypertension is associated with lower plasma renin activity than is the early phase. It is not clear to what extent this reduced plasma renin activity reflects diminished influence of the renin-angiotensin system. It also is not clear whether this change in the character of the disease influences the effectiveness of surgical removal of the renal artery stenosis in reversing hypertension. Using an animal model of sustained (≥10 weeks after renal artery clipping) two-kidney, one-clip renovascular hypertension, we hypothesized that the magnitude of the depressor response to selective angiotensin II receptor blockade with losartan would reflect the influence of the renin-angiotensin system on hypertension and enable us to predict the depressor response to subsequent surgical removal of the clip. Methods: The left renal arteries of 20 male Sprague-Dawley rats weighing 150 to 200 gm were fitted with a silver clip (0.23 mm internal diameter). Systolic blood pressure was measured by means of tail-cuff plethysmography for 10 weeks. Rats were then given losartan orally (30 mg/kg a day) for 1 week while blood pressure was monitored. After an additional week to allow recovery, 13 rats underwent surgical unclipping, and seven underwent sham repair. Blood pressure again was monitored over the final week. Results: All two-kidney one-clip rats had hypertension 10 weeks after clipping (mean systolic blood pressure 206 ± 10 mm Hg). Losartan decreased systolic blood pressure by 36 ± 6 mm Hg. The response was variable, ranging from 3 to 66 mm Hg, and overall blood pressure did not normalize (170 ± 8 mm Hg). Subsequent surgical unclipping decreased systolic blood pressure by 46 ± 9 mm Hg. Again the response was variable, ranging from 10 to 99 mm Hg, although overall blood pressure did not normalize (164 ± 7 mm Hg). The decrease in blood pressure after unclipping showed a high correlation with the blood pressure decrease after losartan administration ( r = 0.861, p < 0.001). Resting plasma renin activity (before intervention) was 16 ± 4 ng angiotensin I per milliliter per hour and was not predictive of the response to either losartan or surgical unclipping. The rats subjected to sham operations had no statistically significant changes in blood pressure. Histologic evaluation showed patent renal arteries without appreciable stenosis or intimal hyperplasia after removal of the clips. Conclusions: In sustained two-kidney, one-clip renovascular hypertension, the depressor response to angiotensin II receptor blockade is attenuated, suggesting that late-phase hypertension becomes increasingly angiotensin II-independent. In our model, the extent to which sustained renovascular hypertension becomes refractory to 7 days of angiotensin II blockade is highly predictive of the ultimate outcome of surgical repair of renal artery stenosis. (J Vasc Surg 1998;28:167-77.)

DD genotype of the angiotensin I-converting enzyme gene is a risk factor for early onset of essential hypertension in Japanese patients

Although angiotensin-converting enzyme (ACE) plays an important role in blood pressure regulation, no relationship between the insertion/deletion (I/D) polymorphism of the ACE gene and essential hypertension has been observed. However, as the pathogenesis and genetic background of essential hypertension are heterogeneous, we investigated whether the ACE gene is a marker of subgroups of patients with essential hypertension. A group of 178 patients with essential hypertension (90 men/88 women; 53 ± 13 years of age, mean age ± SD) and 101 normotensive control subjects (54 men/47 women; 51 ± 14 years of age, mean age ± SD ) were included in the study. The allele frequencies of the two groups were similar. There were no differences in age, blood pressure, retinopathy grade, presence of proteinuria, or resting plasma renin activity (PRA) among the hypertensive patients with the II, ID, and DD genotypes. However, the age of onset of hypertension of patients with the DD genotype was lower ( p < 20.05) and their left ventricular mass index was higher ( p < 20.05) than those in patients with the non-DD genotype. These data suggest that the I/D polymorphism of the ACE gene is associated with an early onset of hypertension and left ventricular hypertrophy in Japanese patients with essential hypertension.

Role of kinins in basal and furosemide-stimulated renin secretion.

There is evidence that kinins contribute to some of the renal, cardiovascular, and endocrine effects of the diuretic furosemide. The aim of the present study was to investigate the role of kinins in the regulation of renin secretion, blood pressure, and heart rate under resting conditions and after administration of furosemide. The effects of icatibant, a potent, specific, and long-lasting bradykinin B2 receptor antagonist, on resting renin secretion, blood pressure, and heart rate, and on the responses of these variables to administration of furosemide, were investigated in conscious, chronically prepared rabbits. Injection of icatibant in doses of 0.1 and 1.0 mg/kg blocked the hypotensive response to intravenous injections of bradykinin completely. The lower dose of icatibant decreased plasma renin activity in some animals, but did not alter their blood pressure or heart rate. The higher dose suppressed resting plasma renin activity from 10.2 +/- 2.2 to 5.6 +/- 1.4 ng/ml/2 h (P < 0.01), without changing the blood pressure or heart rate. Injection of furosemide (2 mg/kg) caused a sustained increase i plasma renin activity from 6.7 +/- 1.6 to 15.9 +/- 3.3 ng/ml/2h (P < 0.01), a transient increase in mean arterial pressure from 72 +/- 3 to 78 +/- 3 mmHg (P < 0.05), and a sustained increase in heart rate from 228 +/- 8 to 253 +/- 6 bpm (P < 0.01). Neither dose of icatibant altered the cardiovascular and renin responses to furosemide. These results provide evidence that bradykinin B2 receptors participate in the regulation of resting renin secretion, but not in the renin secretory or heart rate responses to furosemide.

Exercise-induced proteinuria is attenuated by indomethacin

The role of the prostaglandin (PG) and renin-angiotensin hormonal systems in exercise-induced proteinuria following 30 min of submaximal, steady-state exercise was evaluated. Eight healthy males performed cycle ergometry at 75% of VO2peak on three occasions after the administration of a placebo (PLACEBO), a prostaglandin inhibitor (indomethacin, INDO), and an angiotensin converting enzyme inhibitor (captopril, CAPTO). Urine and blood samples were collected prior to, immediately following exercise, and over 40-min recovery. Data were evaluated for differences among drug treatments and measurement phases. During PLACEBO, exercise increased total protein excretion from 64.9 +/- 9.5 to 408.6 +/- 160.8 micrograms.min-1 (P < 0.05). PG inhibition with INDO significantly attenuated the increased proteinuria due to exercise (149.2 +/- 64.0 micrograms.min-1). The proteinuric response to exercise was not altered by CAPTO. Resting plasma renin activity (PRA) and aldosterone (ALDO) were significantly reduced during the INDO trial. Although the twofold increment in ALDO with exercise remained intact during the INDO trial, the PRA response to exercise was significantly blunted. No treatment differences were observed for mean arterial pressure, sodium excretion, urine flow, or creatinine clearance values during rest or exercise. These results suggest that the proteinuria associated with steady-state exercise is PG dependent and not related to hemodynamic influences.

The relationship between diuretic dose, and the haemodynamic response to captopril in patients with cardiac failure.

The effect of diuretic dose on the haemodynamic response to captopril was assessed in nine patients with chronic cardiac failure. Each patient was given an intravenous dose of captopril while maintained on (a) a low dose diuretic regime, and (b) a high dose diuretic regime. Activity of the renin angiotensin aldosterone system, as assessed by plasma concentrations of these hormones, was greater when patients were receiving the higher dose diuretic regime. The magnitude of haemodynamic response produced by intravenous captopril was greater when the patients were maintained on the high dose diuretic regime, although no significant correlation was found between resting plasma renin activity and resting plasma angiotensin II concentration and the change produced by captopril in any haemodynamic response on either diuretic regime. An increased dosage of loop diuretic potentiates the haemodynamic effects of captopril in patients with cardiac failure. Reduction of diuretic dose prior to introduction of captopril may protect against severe first dose hypotension.

Regulation of intakes of water and NaCl solutions in Fischer 344 rats: Contrasts and comparisons between strains

We present an overview of the differences in intakes of both water and NaCl between different strains of rat, with emphasis on Fischer 344 (F344) and Sprague-Dawley (SD) strains. Relative to SD, rats of the F344 strain show less spontaneous or secondary drinking both with food present and during food deprivation. The water intake of rats of the F344 strain is strongly inhibited when water is added to their food, but rats of the SD strain show less inhibition and consume excessive amounts of fluid. In studies of primary drinking, induced by treatment with various dipsogens, rats of the F344 strain consumed water in amounts that were generally comparable to those expected from rats of the SD strain, with the exception of reduced intakes in response to either polyethylene glycol-induced hypovolemia or treatment with isoproterenol. The hematocrit ratio, resting plasma renin activity and directly-measured plasma protein concentrations were similar between F344 and SD strains. We also review findings that rats of the F344 strain show no spontaneous preference for dilute NaCl solutions, and show that both a strong preference and a low preference threshold are induced by chronic treatment with ramipril. Other manipulations that induce an appetite for NaCl in the F344 strain are summarized.

Chronic dietary administration of tryptophan prevents the development of deoxycorticosterone acetate salt induced hypertension in rats.

Hypertension developed within 3 to 5 weeks in uninephrectomized rats administered deoxycorticosterone acetate (DOCA) at a dose of 850 micrograms X kg-1 X day-1 via Silastic tubes and given isotonic saline to drink. Chronic dietary administration of tryptophan (25 and 50 g/kg of food) to DOCA-treated rats reduced their exaggerated intake of NaCl solution and attenuated the elevation of blood pressure induced by treatment with DOCA alone. Treatment with tryptophan also protected against the reduction in urinary concentrating ability during a 24-h dehydration that is characteristic of DOCA-treated rats. Other tests assessed the responsiveness to the beta-adrenergic agonist, isoproterenol. These included measurement of drinking and heart rate following acute administration of isoproterenol. The characteristically depressed drinking and chronotropic responses of DOCA-treated rats to acute administration of isoproterenol were unaffected by tryptophan. Responsiveness to angiotensin II (AII) was also tested by assessment of dipsogenic and metabolic responses to acute administration of AII. The increased drinking and tail skin temperature responses to administration of AII, characteristic of DOCA-treated rats, were reduced in a graded fashion by treatment with graded doses of tryptophan. The specific binding of AII to its receptors in membranes form the diencephalon of the brain was increased by treatment with DOCA but was returned to control level by concomitant treatment with tryptophan. The content of serotonin in the mesencephalon of the brain was not changed significantly by treatment with tryptophan, but the content of 5-hydroxyindole acetic acid in the same region increased significantly, suggesting that turnover of serotonin was increased by chronic treatment with tryptophan. The cardiac hypertrophy characteristic of treatment with DOCA was attenuated significantly by chronic treatment with tryptophan, while the low, resting plasma renin activity of the DOCA-treated group was unchanged. These results suggest that tryptophan provides significant protection against the development of DOCA-induced hypertension, polydipsia, polyuria, and cardiac hypertrophy in rats. It also reduces the hyperresponsiveness to treatment with AII, possibly by decreasing the specific binding of AII to its receptors. It also appears to increase the turnover of serotonin in the brain. Whether either one or all of these is responsible for the antihypertensive effect of tryptophan remains for further study.

Erythrocyte 2,3-diphosphoglycerate and serum enzyme concentrations in trained and sedentary men

The acute effect of exercise on the intraerythrocyte 2,3-diphosphoglycerate concentration and on various serum enzymes and some related variables was investigated in 14 male athletes before and after a 50-min cross-country run and compared at rest to 15 sedentary subjects. Compared to the sedentary subjects, the athletes had higher resting levels of serum creatine phosphokinase, plasma myoglobin, and renin substrate but had a lower plasma renin activity. The red blood cell 2,3-diphosphoglycerate concentration increased after exercise in the runners and was not different at rest between the athletes and the sedentary subjects. Our data therefore suggest that the resting plasma renin activity is reduced in athletes when compared to sedentary subjects. Training seems however not to alter the resting level of 2,3-diphosphoglycerate in the red blood cells.

Plasma renin activity and forearm blood flow in paraplegic humans.

We recently found that paraplegic humans respond to hyperthermia with subnormal increase in skin blood flow (SkBF), based on measurements of forearm blood flow (FBF). Is this inhibition of SkBF a defect in thermoregulation or a cardiovascular adjustment necessary for blood pressure control? Since high resting plasma renin activity (PRA) is found in unstressed individuals with spinal cord lesions and since PRA increases during hyperthermia in normal humans, we inquired whether the renin-angiotensin system is responsible for the attenuated FBF in hyperthermic resting paraplegics. Five subjects, 28-47 yr, with spinal transections (T1-T10), were heated in water-perfused suits. Blood samples for PRA determinations were collected during a control period and after internal temperature reached approximately 38 degrees C. Some subjects with markedly attenuated FBF had little or no elevation of PRA; those with the best-developed FBF response exhibited the highest PRA. Clearly, circulating angiotensin is not the agent that attenuates SkBF. Rather, increased activity of the renin-angiotensin system may be a favorable adaptation that counters the locally mediated SkBF increase in the lower body and thus allows controlled active vasodilation in the part of the body subject to centrally integrated sympathetic effector outflow.

The effect of angiotensin converting enzyme inhibition on coronary blood flow and hemodynamics in patients without coronary artery disease

We examined the role of the renin-angiotensin system in the regulation of systemic and coronary vascular tone by studying the effect of converting enzyme inhibition by teprotide on systemic and coronary hemodynamic parameters in 14 normal patients undergoing routine cardiac catheterization. Serial hemodynamic measurements were made before and up to 30 minutes after 1 mg/kg of intravenous teprotide. A significant rise in cardiac index and stroke volume index occurred with a fall in systemic vascular resistance. The increase in cardiac index was related to the level of resting plasma renin activity. Blood pressure, pulmonary artery and left ventricular end-diastolic pressures remained unchanged. Coronary sinus thermodilution blood flow also showed no significant change; however, some patients demonstrated dramatic increase in flow. The change in blood flow was highly correlated with the resting plasma renin activity ( r = 0.939 P < 0.001). The change in coronary vascular resistance and myocardial oxygen consumption were likewise related to the resting plasma renin level. Converting enzyme inhibition produces significant systemic hemodynamic changes in normal patients which implies that the renin-angiotensin system is important in normal cardiovascular homeostasis. The direct relationship between plasma renin activity and coronary blood flow suggests that the renin-angiotensin system may play an important role in coronary vasomotor regulation.

The relationship between ambulatory blood pressure and echocardiographically assessed left ventricular hypertrophy.

1. Continuous intra-arterial ambulatory monitoring of blood pressure was recorded in 46 patients with mild to moderate hypertension under standardized conditions. M-mode echocardiography was performed after recording and left ventricular mass index calculated by standard formulae. 2. Systolic blood pressure from continuous recording was significantly correlated with left ventricular mass index (mean 24 h: r = 0.543, n = 45, P less than 0.001). Diastolic blood pressure exhibited a weaker but still significant correlation with left ventricular mass index (mean 24 h: r = 0.318, n = 45, P less than 0.05). Casual systolic blood pressure was significantly correlated with left ventricular mass index (r = 0.476, n = 46, P less than 0.001) but casual diastolic blood pressure did not correlate with left ventricular mass index (r = 0.245, n = 46). Awake blood pressure variability, age, resting plasma renin activity and resting plasma noradrenaline levels did not have a significant correlation with left ventricular mass index. 3. Nine patients were treated for 16 weeks with once-daily timolol and repeat ambulatory monitoring and M-mode echocardiography was performed with the same protocol. 4. Once-daily timolol provided good 24 h control of blood pressure and repeat echocardiography showed a reduction in left ventricular mass index in that group of patients (t = 2.59, P less than 0.05).

Effect of the angiotensin antagonist saralasin on hemodynamics in hypertensive non-uraemic chronic renal disease.

The effect of an intravenous infusion of saralasin in a rising dosage on blood pressure, central haemodynamics, forearm blood flow and venous distensibility was tested in 11 subjects with chronic non-uraemic renal disease. Only 1 subject had an elevated resting plasma renin activity, and in him saralasin produced a drop in systolic and diastolic blood pressures due to a decrease of the total peripheral vascular resistance whereas the plasma renin activity markedly rose. Among the remaining 10 subjects, whose plasma renin activity was within the normotensive range, blood pressure rose transiently in 3, with the lowest dose of aralasin, due to an increase in the total peripheral vascular resistance. Both these parameters returned to the control level when continuing the infusion and increasing its dosage. Excluding this initial period from the analysis, no relevant change, even with a more than tenfold increase in the saralasin dosage and a duration of the infusion of 1 h, was found in the following: blood pressure, cardiac and stroke index, heart rate, total peripheral vascular resistance, central and peripheral venous pressures, forearm blood flow and vascular resistance, forearm blood volume and venous distensibility. The haemodynamic response to the Valsalva manoeuvre remained unaffected by saralasin. It is concluded that angiotensin plays an active role in changing the haemodynamics and in elevating the blood pressure in subjects with chronic non-uraemic renal disease only in those cases where plasma renin activity is raised.

Blockade of isoprenaline-induced changes in plasma free fatty acids, immunoreactive insulin levels and plasma renin activity in healthy human subjects, by propranolol, pindolol, practolol, atenolol, metoprolol and acebutolol.

Abstract 1 The effects of intravenously administered propranolol 0.01 and 0.03, pindolol 0.001 and 0.003, practolol 0.12 and 0.36, atenolol 0.03 and 0.09, metoprolol 0.045 and 0.135 and acebutolol 0.12 and 0.36 mg/kg, on isoprenaline-induced changes in heart rate, blood pressure, plasma free fatty acids, immunoreactive insulin plasma levels and plasma renin activity were determined in six healthy human subjects. 2 Propranolol, atenolol and metoprolol had a stronger effect on resting heart rate than practolol, acebutolol and pindolol, probably reflecting differences in intrinsic β-sympathomimetic activity. Antagonist potencies against isoprenaline-induced changes in heart rate and blood pressure suggested cardioselectivity for practolol, atenolol, metoprolol and the lower dose of acebutolol and non-cardioselectivity for propranolol, pindolol and the higher dose of acebutolol. 3 All six β-adrenoceptor blocking agents were able, to a varying extent, to antagonize the isoprenaline-induced increases in plasma free fatty acids and plasma immunoreactive insulin levels. In general, the cardioselective agents were relatively less effective antagonists than the non-cardioselective agents. 4 Resting plasma renin activity was reduced by all six β-adrenoceptor blocking agents, suggestive of the presence of β1-adrenoceptors mediating renin release, but the non-cardioselective agents propranolol and pindolol seemed relatively more effective in antagonizing isoprenaline-induced increases in plasma renin activity than the cardioselective agents, which indicates that β2-adrenoceptors might also be involved. 5 The results are compatible with the hypothesis that both β1- and β2-adrenoceptors are involved in the regulation of lipolysis, insulin release and renin release.

Low Renin Hypertension - Is It a Stage of Essential Hypertension?

Resting plasma renin activity (PRA) and PRA after the load of furosemide i. v. and two-hour's upright posture were studied on 139 healthy normotensive subjects and 200 patients with essential hypertension. Regarding the age factor, the estimated values in control subjects were very low in the advanced ages over 60 years, while no significant differences were found in the subjects aged from 20 to 59 years. In essential hypertension, a similar relationship between renin and aging was observed. The patients with essential hypertension were classified into 3 groups according to the resting PRA values; low, normal and high. There were no signi-ficant differences among the. 3 groups concerning the mean ages and the blood pressure. Regarding the incidence of low PRA hypertension at different ages there were no significant differences among the decades ander 60 years of age. On the other hand, all hypertensive patients were classified into 3 groups according to their responses of renin secretion; low responders, normal responders, and high res-ponders. There was a positive correlation between the incidences of hyporesponders of renin secretion and the age. Higher incidences of hyporesponders were obtained in older patients. The incidence of hyperresponders was higher in younger patients than in older patients. Our study revealed that the incidences of low resting PRA were similar in each decade under 60 years, and it seems unlikely that low renin hypertension is a stage in a long-term course of essential hypertension. On the contrary, the hyporesponders of renin secretion to the load are apparently related to the age. It is concluded that low PRA essential hypertension must be distinct from the hyporesponder of renin secretion.

Pathophysiologic significance of “stress” or relative polycythemia in essential hypertension

Fourteen patients with essential hypertension (blood pressure 167 ± 2 106 ± 2 [ mean ± standard error of the mean] mm Hg ) were studied prospectively to determine the pathophysiologic correlates of their “stress” or relative polycythemia. All patients had a high hematocrit level (53.1 ± 0.4 vol percent), contracted plasma volume (16.2 ± 0.4 ml/cm height) and normal red cell mass and serum erythropoietin levels. Blood and plasma viscosity (0.076 ± 0.005 and 0.017 ± 0.001 poise, respectively) were increased, and plasma renin activity in the supine, resting state averaged 1.8 ± 0.3 ng/ml per hour. All patients were treated with methyldopa to achieve normal arterial pressure and the previous determinations were repeated after 1 and 4 weeks of treatment. Reduction of pressure was associated with expansion of plasma volume ( P < 0.001) and significant decreases in hematocrit, blood and plasma viscosity and resting plasma renin activity ( P < 0.001). Red cell mass and serum erythropoietin levels remained unchanged. Therefore, the so-called stress polycythemia is a pathophysiologic manifestation of the hypertensive vascular disease in which the abnormal hemodynamic and rheologic alterations can be reversed by antihypertensive therapy. The significance of this reversal may have some bearing upon the high prevalence rates of severe cardiovascular complications associated with so-called stress polycythemia and high renin essential hypertension.