Renin-hyporesponsiveness in essential hypertension dissociation between plasma renin and catecholamines or aldosterone following furosemide

Summary The influences of sequential stimulation with upright posture and sodium depletion by intravenous furosemide on blood levels of norepinephrine, epinephrine, dopamine, renin and aldosterone was studied in 26 normal subjects and 45 patients with borderline (N=20) or established (N=25) essential hypertension. Basal 24-h urinary sodium, norepinephrine and epinephrine excretion rates and basal (supine) plasma catecholamine, renin and aldosterone levels and the body sodium-volume state were comparable between the three groups. Assumption of the upright posture for 10 to 60 min caused significant increases in plasma norepinephrine (P<0.001), epinephrine (P<0.001) or dopamine (P<0.05) levels. Upright plasma catecholamine concentrations were similar in normal and hypertensive subjects and they were not modified further by furosemide. In contrast upright posture as well as furosemide induced each a successive significant (P<0.02) increase in plasma renin and aldosterone levels. Furosemide-stimulated renin was significantly (P<0.05) lower in patients with established hypertension than in normal or borderline hypertensive subjects; however, plasma aldosterone levels were comparable. These findings suggest that renin release induced by furosemide is not mediated by increased adrenergic activity. Consequently, renin-hyporesponsiveness in established hypertension cannot be explained by decreased sympathetic activity. In contrast to the altered renin regulation, aldosterone-responsiveness to upright posture or furosemide as well as adrenergic activity under these conditions appear to be usually normal in borderline or established hypertension.Supported by the Swiss National Science Foundation     

Plasma renin activity,serum aldosterone concentration and selected organ damage indices in essential arterial hypertension

IntroductionThe aim of this study was to assess the relations between plasma renin activity (PRA), serum aldosterone concentration (ALDO) and selected asymptomatic organ damage (AOD) indices in mild primary arterial hypertension (AH).Material and methodsWe measured PRA, ALDO, and selected AOD indices (carotid-femoral pulse wave velocity (cfPWV), central aortic pulse pressure (cPP), estimated glomerular filtration rate (eGFR)) in 122 patients with untreated AH.ResultsPatients with high PRA (≥ 0.65 ng/ml/h) were characterized by lower plasma sodium and aldosterone to renin ratio (ARR), higher ALDO, but a similar level of AOD indices compared to patients with low PRA. cfPWV (p = 0.04) and cPP (p = 0.019) increased with ARR, while eGFR decreased with ALDO (p = 0.008). Only eGFR was independently correlated with ALDO. In subjects with simultaneously high PRA and ARR values, we found significantly higher cfPWV (p = 0.02) and cPP (p = 0.04) and lower eGFR (p = 0.02) than in those with high PRA but low ARR values.ConclusionsAssessment of the influence of the renin-angiotensin-aldosterone system (RAAS) on AOD should include the relationship between renin and aldosterone. The PRA itself has no predictive value for AOD. More advanced arterial stiffness and renal impairment are associated with increased PRA and ARR. The RAAS activity might be useful in AOD prediction and hypertension severity assessment.     

Age- and sex-related differences in muscle activation for a discrete functional task

Electromyography (EMG) recordings for a typical 8-h day have indicated that burst activity is greater in old adults compared with young adults; these age-related adaptations might be due to the tasks undertaken. The purpose of the present study was to determine whether EMG burst activity differs between young and old men and women for a discrete task of daily living, and to assess whether the time of day when the task is performed influences the EMG burst patterns. Subjects completed a discrete functional task of a grocery bag carry prior to and following 8 h of daily activity. Surface EMG was recorded from the biceps brachii, triceps brachii, vastus lateralis, and biceps femoris. Spatial and temporal characteristics of the bursts were quantified as a period of EMG activity being greater than 2% maximum EMG and for a duration longer than 0.1 s. Burst activity did not differ between the morning and evening recordings, which indicate that the time of day does not influence burst activity recorded for a discrete task. Although there were no differences in burst number between young (10.9 +/- 1.0) and old (11.4 +/- 0.7) adults, burst duration and area were 3-7 times larger in old adults compared with young adults. The number of bursts in women (7.9 +/- 1.0) were ~85% less compared with men (14.6 +/- 0.7), but burst duration and burst area were approximately three times larger in women compared with men. Thus, older adults demonstrate higher levels of burst activity compared with young adults, and these age-related changes in burst activity are augmented in women.     

Divalent cations in essential hypertension. Relations between serum ionized calcium, magnesium, and plasma renin activity

We studied the relation of plasma renin activity to serum levels of ionized calcium and magnesium in 102 normotensive patients and in 98 patients with essential hypertension who were divided into low-renin, normal-renin, and high-renin groups. Serum magnesium levels were higher in patients with low-renin hypertension and lower in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.025 for both comparisons) or in normotensive controls (P less than 0.005, P less than 0.05, respectively). In contrast, serum levels of ionized calcium were lower in patients with low-renin hypertension and higher in patients with high-renin hypertension than in those with normal-renin hypertension (P less than 0.001, P less than 0.05, respectively) or in normotensive controls (P less than 0.001, P less than 0.05, respectively). Altogether, the range of plasma renin activity in essential hypertension shows a continuous negative correlation with the serum magnesium level (r = -0.60, P less than 0.001) and a positive correlation with the serum ionized calcium level (r = 0.44, P less than 0.001). Accordingly, plasma renin activity in hypertension may reflect or contribute to changes in calcium and magnesium fluxes across cell membranes.     

Plasma renin activity and plasma aldosterone concentration: influence of crying]

The levels of plasma renin activity (PRA) and plasma aldosterone concentration (PAC) have been known to increase by the influence of crying in infants and toddlers, but no precise informations are available. We evaluated the changes of PRA and PAC after crying by comparing values obtained from 30 infants and toddlers within one minute after the onset of crying, as induced by venopuncture, and three and five minutes after continuation of crying (PRA1, PRA3, PRA5, and PAC1, PAC3, PAC5). The age of these subjects ranged from one to thirty months (median sixteen months). PRA1, PRA3 and PRA5 were 4.0 +/- 1.8 ng/ml per hour, 5.5 +/- 2.7 ng/ml per hour, 7.8 +/- 4.2 ng/ml per hour, respectively. PAC1, PAC3 and PAC5 were 210 +/- 110 pg/ml, 231 +/- 118 pg/ml, 269 +/- 145 pg/ml, respectively. Both PRA and PAC increased with elapsing time. The increase in PRA was marked after a short episode of crying, but that in PAC was of a mild degree. When to evaluate the levels of PRA and PAC in infants and children, especially that of PRA, one should take into consideration of the conditions of the subject such as the duration of crying at blood sampling.     

Common variants of the beta and gamma subunits of the epithelial sodium channel and their relation to plasma renin and aldosterone levels in essential hypertension

Background

Rare mutations of the epithelial sodium channel (ENaC) result in the monogenic hypertension form of Liddle's syndrome. We decided to screen for common variants in the ENaC βand γ subunits in patients with essential hypertension and to relate their occurrence to the activity of circulating renin-angiotensin-aldosterone system.

Methods

Initially, DNA samples from 27 patients with low renin/low aldosterone hypertension were examined. The DNA variants were subsequently screened for in 347 patients with treatment-resistant hypertension, 175 male subjects with documented long-lasting normotension and 301 healthy Plasma renin and aldosterone levels were measured under baseline conditions and during postural and captopril challenge tests.

Results

Two commonly occurring βENaC variants (G589S and a novel intronic i12-17CT substitution) and one novel γENaC variant (V546I) were detected. One of these variants occurred in a heterozygous form in 32 patients, a prevalence (9.2%) significantly higher than that in normotensive males (2.9%, p = 0.007) and blood donors (3.0%, p = 0.001). βENaC i12-17CT was significantly more prevalent in the hypertension group than in the two control groups combined (4.6% vs. 1.1%, p = 0.001). When expressed in Xenopus oocytes, neither of the two ENaC amino acid-changing variants showed a significant difference in activity compared with ENaC wild-type. No direct evidence for a mRNA splicing defect could be obtained for the βENaC intronic variant. The ratio of daily urinary potassium excretion to upright and mean (of supine and upright values) plasma renin activity was higher in variant allele carriers than in non-carriers (p = 0.034 and p = 0.048).

Conclusions

At least 9% of Finnish patients with hypertension admitted to a specialized center carry genetic variants of β and γENaC, a three times higher prevalence than in the normotensive individuals or in random healthy controls. Patients with the variant alleles showed an increased urinary potassium excretion rate in relation to their renin levels.     

Age dependence of the response of blood pressure, heart rate and plasma renin activity to captopril in essential hypertension

The acute effects of the converting enzyme inhibitor captopril on blood pressure, heart rate and plasma renin activity were assessed in 53 patients (aged 20-80 years) with mild to moderate essential hypertension under basal conditions. The systolic blood pressure before captopril was elevated in patients in the forties (p less than 0,01) when compared to the younger patients and was positively correlated to the age before (r = 0.32, p less than 0.05) and after (r = 0.32, p less than 0,05) angiotensin converting enzyme inhibition with captopril 25 mg. the drop in systolic (-13%) and diastolic (-10%) blood pressure was significantly greater in patients in the fifties (p less than 0,025 and p less than 0,05 respectively) when compared to younger and older (p less than 0,1) patients. The response of plasma renin activity paralleled the blood pressure response, while heart rate after captopril was not significantly changed in any group. The lack of age dependence of the blood pressure response to captopril and of reflex tachycardia suggests converting enzyme inhibition to be a valuable adjunct for the treatment of essential hypertension in the elderly.     

Personality characteristics and renin in essential hypertension

There may be specific personality differences between some if not all biochemically defined subgroups of patients with essential hypertension. A newly standardized projective test of reactions to frustration, a questionnaire related to such characteristics as aggressiveness and dominance, and a standardized interview were applied to 16 patients with established high renin essential hypertension and 21 patients of similar age with normal renin. High renin patients are significantly less assertive, fail to externalize their aggression, perceive frustration less and try to please others more; they have a stronger need to solve problems immediately yet tend to deny social conflicts. These tendencies are likely to create internal conflict and indicate a psychosomatic component in high renin essential hypertension.     

Abnormal vasopressin and aldosterone response to furosemide in essential hypertension

Plasma concentrations of arginine vasopressin (AVP), angiotensin II (AII), aldosterone (Aldo), urinary output (V), osmolar clearance (Cosm), free water clearance (CH2O), fractional excretions of sodium (FENa) and potassium (FEK), urinary sodium excretion rate (U-Na) and serum potassium (S-K) were determined in 9 patients with essential hypertension (group I) and 13 normotensive healthy control subjects (group II) before and three times during the first 4 hours after an intravenous injection of 40 mg of furosemide. AVP, AII, Aldo, V, Cosm, FENa, FEK and U-Na increased in both groups. However, the elevation in AVP was significantly more pronounced and the rate of increase in Aldo was significantly slower in group I than in group II. There were no significant differences in AII, V, Cosm, CH2O, FENa, FEK and U-Na between the groups. S-K was significantly reduced only in group I. AVP and AII were not significantly correlated to each other or to blood pressure. It is suggested that the responsiveness of the renal tubules to AVP is reduced in essential hypertension and that the larger increase in AVP might be a compensatory phenomenon. The slower increase in Aldo in essential hypertension could be attributed to the reduction in S-K.     

Circadian variations in plasma renin activity,catecholamines and aldosterone during exercise in women

Summary Four women were studied at 0400 h and 1600 h to determine if their hormonal and hemodynamic responses to exercise varied with the circadian cycle. Esophageal temperature was measured during rest and exercise (60% peak ; 30 min) in a warm room (T _a=35° C; =1.7 kPa). Venous blood samples were drawn during rest and exercise and hemoglobin concentration (Hb), hematocrit (Hct), plasma osmolality (P _osm), plasma protein concentration (P _p), colloid osmotic pressure (COP), plasma renin activity (PRA), cortisol, aldosterone, norepinephrine (NE) and epinephrine (E) were determined. Changes in plasma volume (PV) were estimated from changes in Hb and Hct. The relative hemoconcentration (–11.2%) was similar at 0400 h and 1600 h, but the absolute PV was smaller at 1600 h than at 0400 h (p=0.03). The responses ofP _osm,P _p and COP to exercise were unaffected by time of day. Although PRA was not different at the two times of day, PRA was 244% greater during exercise at 1600 h, but only 103% greater during exercise at 0400 h. The normal circadian rhythms in plasma aldosterone (p=0.043) and plasma cortisol (p=0.004) were observed. Plasma aldosterone was 57% greater during exercise, while plasma cortisol did not change. The change in E and NE was greater at 0400 h, but this was due to the lower resting values of the catecholamines at 0400 h. These data indicate that time of day generally did not affect the hormonal or hemodynamic responses to exercise, with the exception that PRA was markedly higher during exercise at 1600 h compared to 0400 h.