Normal Renin Essential Hypertension Research Articles

Left ventricle remodeling in men with moderate to severe volume-dependent hypertension

We evaluated the influence of increased intravascular volume on the heart anatomy in salt-sensitive types of hypertension, represented by primary aldosteronism (PA) and low-renin essential hypertension (LREH). Echocardiography was performed in 128 males with moderate to severe or resistant hypertension: 44 patients had PA, 40 patients had LREH and 44 patients had normal-renin essential hypertension (NREH). Groups were comparable in demographic characteristics, blood pressure, duration of hypertension and previous antihypertensive treatment. Patients with PA and LREH, in comparison with NREH patients, showed both greater end-systolic (37.6±5.4 and 35.6±4.5 vs 32.6±4.4 mm, p<0.001 and p<0.05) and end-diastolic (56.1±4.5 and 54.0±4.8 vs 50.4±5.1 mm; p<0.001 and p<0.01) left ventricle (LV) diameter. There were no significant differences either in LV wall thicknesses or LV mass, although a higher percentage of patients with PA and LREH met the criteria of eccentric hypertrophy (p<0.001 and p<0.05 respectively). Aldosterone concentration was positively related to LV cavity dimensions, whether wall thicknesses were rather associated with blood pressure levels. In conclusion, plasma volume overload was identified as an important factor influencing LV remodeling in PA and LREH, whether due to excessive aldosterone levels in PA or other pathophysiological mechanisms.

QT interval in patients with primary aldosteronism and low-renin essential hypertension

QT interval prolongation increases the risk of sudden death in several medical conditions. Patients with primary aldosteronism and salt-sensitive hypertension experience more cardiovascular events than those with normal-renin essential hypertension. QT interval prolongation might represent one of the risk factors for cardiovascular events in these patients. The aim of the present study was to evaluate the QT interval in patients with primary aldosteronism and low-renin essential hypertension (LREH). Twenty-seven patients with primary aldosteronism, 17 patients with LREH, 117 patients with essential hypertension and 25 healthy individuals were studied. Plasma aldosterone, plasma renin activity, and aldosterone to plasma renin activity ratio (ARR) were determined. Corrected QT intervals (QTcs) were measured from a 12-lead electrocardiogram. The QTc was longer in primary aldosteronism (434 +/- 23 ms) and LREH (430 +/- 18 ms) compared with essential hypertension (419 +/- 22 ms) and healthy controls (412 +/- 19 ms) (P = 0.0004). The prevalence of QTc longer than 440 ms was higher in primary aldosteronism (48%) and LREH (23%) compared with essential hypertension (11%) and healthy controls (4%) (P < 0.0001). QTc correlated with plasma aldosterone (P = 0.01), ARR (P = 0.02), and diastolic blood pressure (P = 0.01). ARR (P = 0.01) and systolic blood pressure (P = 0.01) were identified as independent predictors of QTc. We postulate that the elevated aldosterone secretion contributes to the prolongation of the QT interval in patients with primary aldosteronism and LREH through both a depletion of intracellular potassium concentration and higher blood pressure values. QTc measurement might represent one simple, non-invasive and reproducible index to characterize the cardiovascular risk in patients with primary aldosteronism and LREH.

High plasma endothelin-1 levels in hypertensive patients with low-renin essential hypertension.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide derived from endothelial cells and may be important in the control of systemic blood pressure (BP) and local blood flow. Immunoreactive ET-1 plasma levels may be normal or elevated in human arterial hypertension, although the exact pathophysiological role of ET-1 remains to be established. The aim of our study was to determine the relationship between the components of the renin-angiotensin-aldosterone system and plasma ET-1 levels in patients with low, normal or high-renin essential hypertension. The study groups included 13 patients with low-renin essential hypertension (average age 43.5 +/- 16.2 years), 16 patients with normal-renin essential hypertension (46.5 +/- 13.4 years), 11 patients with high-renin essential hypertension (40.7 +/- 13.8 years) and 12 healthy subjects (43.1 +/- 11.4 years). Our results demonstrated that the mean ET-1 values of all patients with essential hypertension were 10.4 +/- 3.4 pg/ml; there was not a statistical correlation between plasma renin activity (PRA) and the ET-1 levels of hypertensives; instead there was a statistically significant correlation between plasma ET-1 and plasma aldosterone (PA) (r = 0.393; P < 0.026). In particular mean plasma ET-1 values in patients with low-renin essential hypertension (12.6 +/- 2.1 pg/ml) were significantly higher (ANOVA = 0.000, P < 0.05) than those of normotensive subjects (7.7 +/- 1.7 pg/ml), patients with normal-renin essential hypertension (8.5 +/- 2.8 pg/ml), and patients with high-renin essential hypertension (9.9 +/- 3.8 pg/ml), respectively. There was a statistical correlation between PA and ET-1 levels in patients with low-renin essential hypertension (r = 0.619, P < 0.024). Our study demonstrated that there was an increase of circulating ET-1 levels in patients with low-renin essential hypertension and ET-1 plasma levels correlated with PA. The results suggest that ET-1 may play an important role in this particular form of human essential hypertension.

Modulation of target tissue response to angiotensin II and sodium sensitivity in Japanese patients with essential hypertension.

"Non-modulators" are essential hypertensive patients who fail to modulate an adrenal response, renovascular response, or both, to angiotensin II (Ang II). The aim of the present study was to characterize "non-modulators" among Japanese patients with normal-renin essential hypertension and to determine whether non-modulation is related to sodium sensitivity of blood pressure. The increase in plasma aldosterone concentration (PAC response) and the decrease in renal plasma flow (RPF response) in response to Ang II infusion (3 ng/kg/min) were assessed in 15 Japanese patients with essential hypertension who received a high sodium diet (250 mEq/d) followed by a low sodium diet (10 mEq/d). The subjects were divided into two groups (6 modulators and 9 non-modulators) based on their ability to modulate the PAC response during sodium restriction. There was no significant difference between modulators and non-modulators in electrolyte balance or in plasma Ang II levels on either diet. Changes in the PAC response during sodium restriction were significantly correlated with the change in mean blood pressure during sodium restriction (r = -0.67, p < 0.01), while changes in the RPF response were not. RPF responses in both groups decreased during sodium restriction, although an effect on the RPF response in non-modulators was unexpected. These results suggest that non-modulators do exist among Japanese patients, but that this defect does not involve both the adrenal gland and the kidney. Apparently, only non-modulation of the adrenal response is involved in the mechanism of sodium sensitivity.

Albuminuria in untreated patients with primary aldosteronism or essential hypertension

The determinants and significance of urinary albumin excretion have been studied in normal subjects and in hypertensive patients; however, they are unknown in patients with primary aldosteronism. From a population of 114 patients with documented primary aldosteronism, we selected 23 never-treated patients (12 males, 11 females; 11 tumoral, 12 non-tumoral) and compared them to patients with never-treated essential hypertension with low renin (supine plasma renin activity <1 ng/ml per h, n = 23) or normal renin (supine plasma renin activity between 1 and 4 ng/ml per h, n = 23), matched for age, body mass index, mean arterial pressure, renal function and known duration of hypertension. The patients with primary aldosteronism had lower serum potassium and higher plasma aldosterone concentrations than those with essential hypertension. Urinary albumin and beta2-microglobulin excretion were greater in untreated patients with primary aldosteronism than in those with low- or normal-renin essential hypertension. Among the patients with essential hypertension, the renin activity was not a determinant of albuminuria. These findings indicate that primary aldosteronism is associated with excessive urinary albumin excretion. This albuminuria could be due to impairment of proximal tubular reabsorption caused by hypokalemic nephropathy and/or by high levels of circulating aldosterone; however, it could be an indicator of target-organ damage associated with primary aldosteronism.

Alterations of calcium metabolism and of parathyroid function in primary aldosteronism, and their reversal by spironolactone or by surgical removal of aldosterone-producing adenomas

In order to investigate the possible existence of abnormal calcium metabolism and parathyroid function in primary aldosteronism (PA), we have compared the calcium/parathyroid hormone (PTH) profile of patients with PA with the profile of healthy normotensive subjects and of patients with essential hypertension (EH). Furthermore, we have evaluated the effects of spironolactone and the surgical removal of aldosterone-producing adenomas on the calcium/PTH profile in the PA patients. Four groups of 10 subjects each participated in the study: 1) hypertensive patients with PA, 2) patients with low-renin EH (LREH), 3) patients with normal-renin EH (NREH), 4) normotensive healthy subjects (NS). The four groups were well-matched for age, sex, body mass index, and renal function. The three hypertensive groups were also matched closely for blood pressure values and for duration of hypertension. In all subjects, after 1 week of a controlled intake of Na and K, the following parameters were measured: urine excretion of Na, K, Ca, Mg, and P, plasma levels of K, Mg, inorganic P, total calcium and ionized calcium, and plasma renin activity, aldosterone concentration, and intact PTH. Blood pressure and laboratory parameters were determined again in all the PA patients after 1 month of 100 mg daily spironolactone administration, and in four out of the 10 PA patients 2 months after surgical removal of aldosterone-producing adenomas. All of these subjects had undergone the same controlled intake of Na and K indicated above. Serum intact PTH was higher in PA patients than in the other three groups (P < .01), and serum ionized calcium was significantly higher in normotensive subjects than in the three hypertensive groups (v PA P < .01, v LREH and v NREH P < .05). An increase in serum ionized calcium and a decrease in PTH level were associated with both spironolactone administration (P < .001) and surgical treatment (P < .05). These results suggest the presence of calcium metabolism alterations in both PA and EH patients, but that these alterations are more exaggerated in PA, so that higher PTH levels are needed for maintaining low-normal levels of serum ionized calcium.

Plasma 19‐hydroxyandrostenedione is elevated in patients with high renin essential hypertension

We have reported that 19-hydroxyandrostenedione (19-OH-A-dione) functions as an amplifier of the sodium-retaining and hypertensive action of aldosterone. We therefore measured 19-hydroxyandrostenedione in hypertensive patients. We studied 53 normal male control subjects and 63 male patients with essential hypertension (48 patients with normal renin essential hypertension and 15 patients with high renin essential hypertension). Plasma 19-OH-A-dione levels were measured by RIA. Plasma 19-OH-A-dione concentrations in control subjects and patients with normal and high renin essential hypertension were 115 +/- 46 (mean +/- SD), 112 +/- 49 and 201 +/- 79 pmol/l, respectively. Patients with high renin essential hypertension showed significantly higher 19-OH-A-dione concentrations than did control subjects. The evaluation of the correlation between plasma 19-OH-A-dione concentrations and plasma renin activity revealed that plasma 19-OH-A-dione concentrations in hypertensive subjects rose gradually with an increase in plasma renin activity. Therefore, a significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.586, P < 0.001). In contrast, in control subjects, no significant correlation was found between plasma renin activity and plasma 19-OH-A-dione (r = 0.059, P > 0.05). The secretion of 19-OH-A-dione from the adrenal cortex is under the control of the renin-angiotensin system in hypertensives but not in normotensives.

Salt and hypertension: water-sodium handling in essential hypertension.

This paper describes sodium handling in the kidney and the significance and mechanisms of its effects upon essential hypertension. In patients with low renin essential hypertension, plasma and urinary norepinephrine levels, plasma renin activity and fractional excretion of sodium were significantly lower, while plasma volume, extracellular fluid volume and exchangeable sodium were higher than in normal renin essential hypertension. The suppression of some renal depressor-natriuretic systems, the dopaminergic, kallikrein-kinin and prostaglandin E2 systems may contribute to the retention of sodium-water in these patients, because these depressor systems were observed to be greatly suppressed in essential hypertension, especially in the low renin group. The reduction of conversion from L-dopa to dopamine by dopa-decarboxylase in the proximal tubules was suggested from our clearance studies as the mechanism of the suppression of renal dopaminergic activity. Moreover, renal dopaminergic activity was already suppressed at the prehypertensive stage, possibly through the inhibition of renal dopa-decarboxylase activity. Thus, it appears that the suppression of renal depressor-natriuretic systems play an important role in the pathogenesis of essential hypertension through the retention of sodium and body fluid volume.

High urinary dopa and low urinary dopamine-to-dopa ratio in salt-sensitive hypertension.

Dopamine in urine is derived substantially from renal uptake and decarboxylation of 3,4-dihydroxyphenylalanine (dopa), and increases in excretion of dopa normally parallel increases in excretion of dopamine during salt loading. Since patients with salt-sensitive hypertension may have decreased urinary excretion of dopamine during dietary salt loading, the present study was designed to evaluate the response of dopa to salt loading. Sixteen inpatients with normal-renin essential hypertension ate a constant metabolic diet containing 9 mmol/day sodium for 7 days, followed by the same diet but containing 249 mmol/day sodium for 7 days. Salt sensitivity was defined as an increase in mean arterial pressure of 8 mm Hg between the diets; on this basis, nine patients were salt-sensitive and seven, salt-resistant. The rate of urinary dopa excretion was significantly higher in the salt-sensitive patients throughout the study (mean rates 132 +/- 13 nmol/day in the salt-sensitive group and 78 +/- 9 nmol/day in the salt-resistant group for the 14 days of observation, p less than 0.01). When dietary sodium intake was increased to 249 mmol/day, urinary dopa excretion increased significantly more in salt-sensitive patients than salt-resistant patients. At the end of the high salt diet, dopamine excretion was significantly attenuated in the salt-sensitive patients, despite higher rates of dopa excretion. Thus, the urinary ratio of dopamine to dopa was decreased in salt-sensitive patients, regardless of salt intake.(ABSTRACT TRUNCATED AT 250 WORDS)

Renal Function in One-Kidney, One-Clip Hypertension and Low Renin Essential Hypertension

One-kidney, one-clip hypertension (1-K, 1-C HT) is initiated by increased preglomerular resistance which decreases nephron perfusion and causes several intrarenal changes that lead to increased mean arterial pressure (MAP). Elevated MAP serves to return nephron perfusion and sodium excretion to normal, so that fluid intake and output are balanced. Increased MAP usually occurs through volume homeostasis mechanisms that initially raise cardiac output and later elevate total peripheral vascular resistance via autoregulatory adjustments. However, if adequate volume is unavailable because of sodium restriction, sustained activation of the renin-angiotensin system increases blood pressure sufficiently to restore nephron perfusion. Thus, depending upon the availability of volume, renal perfusion and sodium balance can be restored either by volume retention or by increased angiotensin II (ANGII) formation and peripheral vasoconstriction. Similarities exist between 1-K, 1-C HT and low-renin essential hypertension (LRHT). In both cases, renal-pressure natriuresis is shifted to higher levels and there are marked increases in preglomerular resistance that necessitate increased MAP to maintain sodium balance. However, in 1-K, 1-C HT, there is a parallel shift of pressure natriuresis with little or no change in the slope of this curve, similar to that found in the normal-renin essential hypertension. In LRHT the slope of pressure natriuresis is decreased, indicating that blood pressure is much more salt sensitive than normal. Another difference is that PRA is low compared to normal PRA in 1-K, 1-C HT after compensatory increases in MAP. There is also no indication of glomerular membrane damage in 1-K, 1-C HT, whereas LRHT may have significant glomerulopathy, especially as hypertension progresses. These differences suggest that there may be additional factors besides preglomerular vasoconstriction involved in the etiology of LRHT. One possible factor is a reduction in nephron number in LRHT. Decreased functional nephrons would lead to glomerular hyperfiltration and increased distal tubular flow rate in the remaining nephrons, causing decreased PRA and eventually glomerular damage. Increased fractional sodium reabsorption, particularly in distal tubular segments, could also contribute to decreased PRA and cause blood pressure to be salt sensitive. These abnormalities, along with preglomerular vasoconstriction, may explain many of the characteristics of LRHT.

Dissociation of Plasma Atrial Natriuretic Peptide Responses to Upright Posture and Furosemide Administration in Patients with Normal-, Low Renin Essential Hypertension and Primary Aldosteronism

Plasma levels of atrial natriuretic peptide (ANP) were measured in patients with normal renin essential hypertension (n = 12), low renin essential hypertension (n = 11) and primary aldosteronism due to aldosterone producing adenoma (APA, n = 8) and idiopathic hyperaldosteronism (IHA, n = 3) after overnight rest in the supine position and after 4 h upright posture and furosemide administration. Plasma renin activity (PRA) and aldosterone (Aldo) levels were also determined. Compared to normal renin essential hypertension (33.6 +/- 2.2 pg/ml), basal plasma ANP was significantly higher in low renin essential hypertension (66.8 +/- 6 pg/ml), IHA (54.1 +/- 6.3 pg/ml) and APA before (62.4 +/- 4.9 pg/ml) but not after adrenal surgery (22 +/- 3 pg/ml). After upright posture and furosemide administration plasma ANP was decreased (p less than 0.01) in patients with low renin and, less markedly, with normal renin essential hypertension, however not in IHA and APA. In about half of the patients with low renin essential hypertension, unchanged PRA after upright posture and furosemide administration was associated with increased plasma Aldo and decreased ANP levels. We conclude that (i) the relatively high basal plasma ANP levels in low renin essential hypertension, IHA and APA may reflect the presence of volume expansion in these patients; (ii) the hormonal responses to upright posture and furosemide administration in patients with normal and low renin essential hypertension may indicate a counterregulatory role of ANP during activation of the renin-angiotensin-aldosterone system; (iii) the high plasma ANP, which is unresponsive to upright posture and furosemide administration, in patients with APA and IHA may be a potentially interesting new finding whose pathophysiological significance remains to be established.

The significance of atrial natriuretic polypeptide in the cause of essential hypertension

The study was undertaken to clarify the role of atrial natriuretic polypeptide (ANP) in essential hypertension (EH). Plasma levels of alpha-human ANP (alpha hANP) were measured in 13 normal subjects, 25 patients with EH, 5 patients with primary aldosteronism (PA), 3 patients with renovascular hypertension (RVH) and 3 patients with pheochromocytoma (PC). Plasma level of alpha hANP (normal: 38.1 +/- 20.5pg/ml) was high in all hypertensive subjects. Synthetic alpha hANP was intravenously administrated to these subjects as follows: first a dose of 0.01 microgram/kg/min for 30 minutes, second a dose of 0.03 microgram/kg/min for 30 minutes, and then in normal subjects and EH 0.03 microgram/kg/min with a dose of 6.5 micrograms/kg/min of metoclopramide (MC) for 30 minutes. After the infusion of 0.01 microgram/kg/min alpha hANP, arterial blood pressure was significantly depressed in EH, RVH and PA, but not in PC. Marked diuretic and natriuretic responses were observed with increase in creatinine clearance and fractional sodium excretion in EH, RVH and PA, but not in PC. Sodium clearance/lithium clearance was slightly increased after infusion of 0.03 microgram/kg/min of alpha hANP in hypertensive subjects. Plasma renin activity did not change in low and normal renin EH and PA after infusion of either dose of alpha hANP, but was suppressed after 0.03 microgram/kg/min of alpha hANP in normal subjects and high renin EH, RVH and PC. Plasma aldosterone concentration was suppressed after either dose of alpha hANP in normal subjects and in EH, RVH and PC, but not in PA. Plasma cGMP concentration and urinary cGMP excretion were decreased after either dose of alpha hANP in both normal and hypertensive subjects. Furthermore, the decrease of PAC by alpha hANP was normalized by MC in normal subjects and EH. The rise in plasma cGMP by alpha hANP was suppressed by MC in both normal subjects and EH, but no changes were observed in arterial blood pressure and natriuretic response. These results suggest that alpha hANP secretion increases with elevation of blood pressure in EH, improving increase of circulatory blood volume, and alpha hANP may play a role in elevating blood pressure in EH. Moreover, it is considered that ANP increases sodium and water excretion through its effect on both renal glomeruli and distal tubules in EH. Hypotensive and natriuretic effects of ANP in EH may be concerned with dopaminergic activity which are probably related to the production of cGMP in the vascular wall and inhibition of the excretion of aldosterone in the adrenal cortex.

Attenuated Renal Production of Dopamine in Patients with Low Renin Essential Hypertension

Our previous studies have shown that a suppressed pressure natriuresis may contribute to the hypertensive mechanism in patients with essential hypertension (EHT), particularly in low renin patients (LRH). In this study, in order to clarify the role of renal dopaminergic activity in the blunted natriuresis of LRH, the conversion of 1-dopa (DOPA) to dopamine (DA) in the kidneys was investigated in 9 normotensive subjects (NT) and 20 EHT, including 15 normal renin EHT (NRH) and 5 LRH. All subjects were hospitalized and received a constant diet (Na:120mEq, K:75mEq daily). Plasma DOPA concentration (p-DOPA:HPLC-ECD), creatinine clearance (Ccr), urinary excretion of sodium (UNaV) and DA (UDA), as well as fractional excretion of sodium (FENa) were measured before and after the single oral administration of 1-DOPA (400mg). DOPA administration caused a significant increase of p-DOPA, UDA and FENa with undetectable DOPA levels in the urine in EHT. In addition, under the basal condition, UDA correlated positively with p-DOPA or the product of p-DOPA x Ccr, which might reflect the DOPA delivery at the renal proximal tubule. No significant difference was found in p-DOPA and the product of p-DOPA x Ccr among NT, NRH and LRH. However, the ratio of UDA/(p-DOPA x Ccr), which may indicate the conversion from DOPA to DA in the kidneys, was lower in EHT, especially in LRH, than that in NT. These results suggest that a reduced renal conversion from DOPA to DA may contribute to the attenuated natriuresis as well as renal dopaminergic activity in LRH.

Renin suppression by saline is blunted in nonmodulating essential hypertension.

We have reported that 50% of subjects with normal renin essential hypertension have both delayed suppression of the renin-angiotensin-aldosterone axis following sodium infusion and a delayed rate of excretion of an acute salt load. In another study we have also described a subset of patients with essential hypertension (called nonmodulators) who have several abnormalities, including a pressor response to salt loading. To evaluate whether the abnormalities described in these different groups of patients actually occur in the same patient, we assessed the renin-angiotensin-aldosterone axis response to short-term saline loading in 38 hypertensive patients. Their ability to modulate was determined by their renal vascular response to infused angiotensin II on a high salt diet (200 mEq Na). In response to a 3-hour infusion of saline, 75 mEq/hr, the reduction in plasma renin activity at both 60 and 120 minutes was significantly greater (p less than 0.008) in patients with normal modulation than in the nonmodulators. Plasma aldosterone levels were also significantly lower (p less than 0.001) in those with intact modulation. Thus, nonmodulating essential hypertensive patients have abnormalities in several systems that influence sodium homeostasis, including altered adrenal and renal vascular response to angiotensin II, altered renal blood flow response to salt loading, and a delayed suppression of the renin-angiotensin-aldosterone system with short-term saline infusion.

Significance of oxytocin to disorders of fluid and electrolyte metabolism in patients with essential hypertension

A possible involvement of oxytocin (OT) has been indicated in regulation of water and electrolyte metabolism, based on findings that the secretion of OT is increased by either water deprivation or sodium loading. However, to date, no informations have yet been obtained about the role of OT in hypertension. The present study was therefore undertaken to elucidate the role of OT for abnormalities of fluid and electrolyte metabolism in essential hypertension (EH) in comparison with normotensive subjects (NT). The major results were as follows. Plasma level of OT was 3.7 +/- 2.1 pg/ml (mean +/- SD) in EH, not significantly higher than that in NT (3.2 +/- 1.7 pg/ml). Plasma OT in low-renin EH (4.8 +/- 2.5 pg/ml) was significantly different from that in high-renin EH (2.9 +/- 1.4 pg/ml, p less than 0.05) and NT (p less than 0.05), but not in normal-renin EH (3.8 +/- 2.0 pg/ml). Plasma OT was inversely correlated with plasma renin activity (PRA) in EH (r = -0.384, p less than 0.01), but not in NT (r = 0.102). No significant correlation was found between plasma OT and plasma aldosterone concentration (PAC), plasma concentration of antidiuretic hormone (ADH), serum sodium and potassium, blood pressure and renal function in either EH or NT. I.m. injection of OT (0.04 IU/kg) increased significantly urinary excretions of sodium and potassium in EH and NT. However, the increment in sodium excretion was greater in low-renin EH than that in normal-renin EH (0.05 less than p less than 0.10), high-renin EH (p less than 0.05) and NT (p less than 0.05). PRA, PAC and ADH were significantly decreased after OT injection, but blood pressure, serum sodium and potassium were not altered in both EH and NT. I.v. administration of OT (0.1 approximately 0.2 IU/min) suppressed angiotensin II-induced increase of PAC and elevation of blood pressure in both EH and NT. The decrease in PAC by the OT administration was the greatest in low-renin EH. The reduction of blood pressure was significantly greater in EH than in NT (p less than 0.05). I.v. administration of hypertonic saline (5%) resulted in a significant increase of plasma OT in EH and NT, and the increment in OT was the greatest in low-renin EH. Serum sodium concentration was increased by the infusion, positively correlated with plasma OT in both EH (r = 0.458, p less than 0.05) and NT (r = 0.830, p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Role of 18-hydroxylated cortisols in hypertension

The isolation of 18-hydroxycortisol and 18-oxocortisol was recently described. These steroids have been shown to be excreted in exaggerated quantities in patients with primary aldosteronism, with adrenal adenomas and in glucocorticoid suppressible aldosteronism. We report the measurement of both steroids in the urine of patients with essential hypertension. 18-Oxocortisol excretion did not differ in patients with normal renin essential hypertension (0.7 ± 0.7 μg/24 h), low renine essential hypertension (0.7 ± 0.5 μg/24 h) and normal individuals (1.2 ±0.9 μg/24 h). Patients with normal renin hypertension excreted 54 ± 43 μg/24 h of 18-hydroxycortisol, those with low renin essential hypertension excreted 58 ± 54 μg/24 h, and normal individuals excreted 63 ± 36 βg/24 h. Three of the low renin and one of the normal renin hypertensive subjects excreted greater quantities of 18-hydroxycortisol than the upper limit of normal, but all excreted normal quantities of 18-oxocortisol. As 18-hydroxycortisol is inactive, the meaning of this elevated excretion is unclear, but it may be a marker of an adrenal enzymatic abnormality which may be playing a more direct role in hypertension.

Increased plasma vasopressin in low renin essential hypertension.

Baseline plasma vasopressin concentrations were measured in 48 men (all 50 years old) with decreased plasma renin concentration and untreated, sustained essential hypertension and in 29 healthy normotensive men. Mean hypertensive plasma vasopressin concentration was more than twice as high as the corresponding normotensive level (15.7 +/- 2.2 [SE] vs 7.5 +/- 1.0 pg/ml; p less than 0.001). Plasma renin concentration in the hypertensive group was reduced compared with that in the normotensive group (0.28 +/- 0.04 vs 0.46 +/- 0.06 Goldblatt units X 10(-4)/ml). These differences appeared despite virtually identical serum osmolality, creatinine clearance, and urinary sodium excretion in the two groups. In the first 38 hypertensive subjects, arterial plasma epinephrine concentrations were significantly increased over those of the first 28 control subjects (99 +/- 12 vs 68 +/- 6 pg/ml; p less than 0.025). In contrast to those with low renin essential hypertension, 35 men with normal renin essential hypertension (all 40 years old) had normal plasma vasopressin levels that were not significantly different from those in a comparable normotensive control group (3.7 +/- 0.8 vs 3.5 +/- 0.4 pg/ml). Arterial epinephrine concentrations were not significantly different between normal renin subjects and the control group. After 6 weeks of treatment with the nonselective beta-adrenergic receptor blocker oxprenolol in 11 subjects with low renin hypertension, blood pressure was reduced and the plasma vasopressin concentration fell from 27.6 +/- 6.4 to 13.5 +/- 4.2 pg/ml (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma prolactin levels in patients with essential hypertension, malignant hypertension and secondary hypertension.

Plasma prolactin level and plasma renin activity were determined in normal subjects and patients with low and normal renin essential hypertension, renal hypertension, renovascular hypertension, primary aldosteronism, Cushing syndrome, pheochromocytoma and malignant hypertension. In both normal subjects and the normal renin essential hypertensives, plasma prolactin was significantly higher in females than in males. Plasma prolactin was also significantly higher in the normal renin essential hypertensives than in normal subjects of both sexes, while no significant difference was found between the low renin group and normal subjects of either sex. A significantly positive correlation was observed between plasma renin activity and the plasma prolactin level in male essential hypertensives, but not in females. Although no significant difference in plasma prolactin level could be detected between patients with secondary hypertension and normal subjects, this level was significantly higher in malignant hypertensives than in normotensives. From these results, it was shown that significant differences of plasma prolactin levels exist between normal renin essential hypertensives, and low renin essential hypertensives or normal subjects, and that these differences may partly depend on renin status which might be related to the central dopaminergic activity. In malignant hypertensives, the high level of plasma prolactin may be caused by diminished renal function, but the suppression of central dopaminergic activity cannot be excluded in the mechanism of plasma prolactin increment.

Prostaglandin excretion after furosemide in normal and low-renin essential hypertension.

We examined the urinary excretion of prostaglandin (PG)E2 and PGF2 alpha before and 15 min after stimulation with the acutely vasodilating agent furosemide in 25 normotensive controls and 81 patients with essential hypertension (EH). After furosemide administration, PGE2 excretion was lower in patients with EH (P less than 0.02). Excretion rates of PGF2 alpha and of sodium, and urinary volume in hypertensive patients were not significantly different from the values found in normotensive controls. Patients with low-renin essential hypertension (LREH) had a significantly reduced excretion of both PGE2 and PGF2 alpha before and after administration of furosemide as compared to controls. The difference in PGF2 alpha excretion was also significant when LREH patients were compared to those with normal-renin essential hypertension (NREH). Patients with LREH were older and excreted less potassium than patients with NREH or normotensive controls. We conclude that the reduced PG excretion immediately after furosemide administration in patients with EH reflects a diminished capacity of the hypertensive kidney to generate prostaglandins which exert an overall vasodilating effect. Since renin secretion is under the control of renal PG formation, the decreased responsiveness of plasma renin activity (PRA) observed in patients with EH and predominantly in those with LREH may be the consequence of a decreased renal cortical PG generation. Alternatively, mechanisms that reduce both PRA and PG generation have to be considered.

Captopril enhances vascular and adrenal responsiveness to angiotensin II in essential hypertension.

The converting-enzyme inhibitor captopril (25-50 mg orally every 6 h for 66 h) was used to dissociate the circulating levels of angiotensin II (ANG II) from changes in sodium balance in 11 patients with normal renin essential hypertension on 10 mmol of sodium/day intake. Pressor, renal vascular and adrenal responses to graded infusions of ANG II (0.3, 1 and 3 pmol kg-1 min-1) were measured before and after captopril administration. Systemic vascular responses were assessed by measuring diastolic blood pressure (DBP), renovascular responses by measuring p-aminohippurate (PAH) clearance and adrenal responses by measuring plasma aldosterone. After receiving captopril for 66 h the hypertensive subjects showed a significantly (P less than 0.004) enhanced blood pressure response to the infused ANG II but not to noradrenaline when compared with the response before captopril. ANG II (3 pmol kg-1 min-1) also produced a significantly (P less than 0.03) greater reduction in PAH clearance after (-194 +/- 40 ml/min) compared with before (-104 +/- 15 ml/min) captopril. These results suggest that the responsiveness to ANG II in these two target tissues is determined by the circulating ANG II level. In the adrenal gland the aldosterone responses to ANG II also were significantly greater after (P less than 0.01) than before captopril (increment at 3 pmol kg-1 min-1: 660 +/- 88 vs 381 +/- 94 pmol/l). These results are in distinct contrast with the responses previously reported for normotensive subjects and support the hypothesis that the regulation of aldosterone secretion is altered in subjects with essential hypertension.