Plasma prolactin, renin and catecholamines in young normotensive and borderline hypertensive subjects

It has been reported that patients with essential hypertension have high plasma prolactin levels and suggested that reduced central dopaminergic activity may be a factor in the pathogenesis of essential hypertension. This study examines the influence of posture on plasma prolactin, plasma catecholamines, plasma renin activity, blood pressure and heart rate in 24 patients with borderline hypertension (age 19 +/- 1 years) and 20 normotensive subjects matched for age and body mass index. Supine plasma prolactin levels were similar in both groups [borderline hypertension, 11.3 +/- 0.7 ng/ml; normotensive, 10.7 +/- 0.8 ng/ml (mean +/- s.e.m.)] and no increase in plasma prolactin was observed after 10 min standing in both groups. Normotensive and borderline hypertensive subjects had similar values for supine and upright plasma renin activity and plasma norepinephrine. There were no significant correlations between supine plasma prolactin and supine blood pressure, supine plasma renin activity or plasma norepinephrine when data from both normotensive and borderline hypertensive subjects were combined. These results may provide indirect evidence against the occurrence of reduced central dopaminergic activity in borderline hypertension.     

Relationships between blood pressure, heart rate and plasma epinephrine, norepinephrine, angiotensin II concentrations, plasma renin activity during chronic guanfacine therapy in patients with essential arterial hypertension

The evolution of blood pressure, heart rate, epinephrine, norepinephrine, angiotensin II and plasma renin activity has been studied in 10 patients with essential arterial hypertension before and during a two months period of treatment with guanfacine, a new centrally acting hypotensive drug. Guanfacine was proven effective in lowering both systolic and diastolic supine and standing blood pressure. A decrease in supine and standing norepinephrine plasma concentrations and plasma renin activity was observed. No change was seen in epinephrine or angiotensin II. The fall in supine blood pressure observed during the treatment period was positively correlated with the change in norepinephrine.     

Alpha and beta adrenergic blockade with orally administered labetalol in hypertension. Studies on blood volume, plasma renin and aldosterone and catecholamine excretion.

Patients with essential hypertension were treated for 6 weeks with the alpha and beta adrenoceptor blocking agent labetalol alone (no. = 18) or in combination with the diuretic agent chlorthalidone (no. = 11). Maximal doses of labetalol during these trials averaged 1,460 and 650 mg/day, respectively. Significant (P < 0.05) changes during therapy with labetalol alone included a transient decrease in supine blood pressure reaching a maximum of 11 percent, persistent reduction in upright blood pressure, pulse rate (20 percent) and plasma renin activity (40 percent), a gain of 1.7 percent in body weight and of 17 percent in blood volume, a sevenfold rise in epinephrine excretion rate and a mild increase in plasma potassium; plasma aldosterone and norepinephrine excretion rate remained unaltered. After 6 weeks of combination therapy, blood pressure reduction was greater (P < 0.02) than after labetalol alone in both the supine (14.4 versus 4.3 percent) and upright (18.6 versus 11.6 percent) positions; blood volume and plasma potassium were decreased (P < 0.05), plasma renin was doubled (P < 0.02) and plasma aldosterone was unchanged. Orthostatic hypotension and several other side effects were common with large doses of labetalol but infrequent at doses used during combination therapy; moreover, these effects were often transient. These data indicate that combined alpha and beta adrenoceptor blockade with labetalol may effectively reduce blood pressure in patients with essential hypertension, with a somewhat more pronounced effect in the upright position. Extracell fluid retention may reduce the sensitivity of supine blood pressure to treatment, but this effect is avoided with concomitant diuretic therapy. Labetalol's antihypertensive action appears to be renin-independent and is associated with a marked increase in epinephrine excretion.     

Neurogenic factors in low renin essential hypertension

The interrelationships between blood pressure, plasma catecholamines and plasma renin activity (PRA) were studied in 12 patients with low PRA, in 18 patients with essential hypertension and normal PRA and in 11 normal subjects, after being supine for 1 hour, standing 1 hour and after the oral administration of furosemide, 80 mg. Patients with low PRA were older and had higher (p < 0.05) mean blood pressure levels (113 ± 4.2 mg Hg) than patients with normal PRA (103 ± 1.9 mm Hg). Plasma norepinephrine levels were 145 ± 14 ng/liter in normal volunteer subjects, 202 ± 25 ng/liter in hypertensive subjects with normal PRA and 203 ± 26 ng/liter in hypertensive subjects with low PRA. The increase of plasma norepinephrine and epinephrine after standing 1 hour and after the administration of furosemide was similar in hypertensive subjects with low or normal PRA and in normal volunteer subjects. However, the increase in PRA after standing or after the administration of furosemide was significantly reduced in patients with low PRA. These data suggest that patients with low PRA have a normally responsive sympathetic nervous system and that the low PRA may be due to a defective renin response to the sympathetic nerve stimulation. Blood pressure was significantly correlated with plasma catecholamines in normal volunteer subjects (r = 0.71, p < 0.05) and in the hypertensive patients (r = 0.49, p < 0.05). An analysis of the regression lines for the two groups suggests that increased vascular reactivity to catecholamines may account for the increased blood pressure at each level of catecholamines in hypertensive subjects as compared to normal volunteer subjects. Basal plasma aldosterone levels were similar in patients with low and with normal PRA.Norepinephrine clearance was lower in hypertensive than in normotensive subjects.     

Contrasting effects of acute beta blockade with propranolol on plasma catecholamines and renin in essential hypertension: a possible basis for the delayed antihypertensive response.

Blood pressure, heart rate, plasma renin activity, plasma norepinephrine and plasma epinephrine were determined in 11 patients with essential hypertension at rest before and 15, 30, 45, and 60 minutes after an intravenous infusion of 0.12 mg./Kg. propranolol given over five minutes. After propranolol mean blood pressure was unchanged; heart rate decreased by 14 per cent within 15 minutes and showed no further changes. Plasma renin activity decreased progressively by 48 per cent 60 minutes after propranolol, whereas plasma norepinephrine and epinephrine were always higher after propranolol than control values. Increases in norepinephrine were statistically significant at 30, 45, and 60 minutes (respectively 49, 39, and 45 per cent, P less than 0.005 at least) and those of epinephrine even at 15 minutes (respectively 60, 82, 62, and 94 per cent P less than 0.01 for all). These results indicate that acute beta blockade with propranolol incudes increases in circulating plasma norepinephrine and epinephrine which might be consequent to rapidly induced hemodynamic changes. This augmented sympathetic activity might explain why propranolol, when acutely infused, does not decrease blood pressure despite effective cardiac and renin blockade.     

Cardiovascular and endocrine profile of adrenergic neurone blockade in normal and hypertensive man.

Some cardiovascular and endocrine effects of adrenergic blockade were assessed in six normal subjects, six patients with mild hypertension (diastolic pressure < 100 mm Hg) and six patients with moderate to severe essential hypertension. Administration of the inhibitory agent, debrisoquine, for six weeks markedly decreased supine and upright plasma norepinephrine levels, and norepinephrine excretion in all three groups. Supine and upright blood pressure was decreased more (p < 0.001) in those with moderate to severe hypertension (15 and 27 per cent) than in those with mild hypertension (6 and 8 per cent) and remained unchanged in normal subjects. Pulse rate and plasma renin levels were lowered (p <0.01) in patients with moderate to severe hypertension, but not in normal or mildly hypertensive subjects. The different influence of blood pressure, pulse rate and renin in the three groups could not be explained by variations in drug dosage, norepinephrine inhibition, age, basal sodium balance or secondary blood volume expansion, the latter being marked in all groups. Diuretic therapy in addition to sympathetic inhibition reversed blood volume expansion, and further augmented the reduction in supine and upright blood pressure in patients with moderate to severe (?21 and ?47 per cent) or mild hypertension (?8 and ?12 per cent). Plasma aldosterone, cortisol and epinephrine values remained unchanged, and no severe or intolerable side effects occurred during treatment. These data suggest that adrenergic neuron blockade with modest doses of debrisoquine, combined with a diuretic, may be an effective and acceptable mode of therapy in patients with either mild or more severe hypertension. The hypotensive, cardiac-slowing and renin-inhibitory potential of adrenergic neuron blockade may be initiated by decreased norepinephrine outflow and modulated by variations in end-organ responsiveness, normal subjects being relatively insensitive and patients with essential hypertension being more sensitive as the severity of their hypertension increases.     

Different antihypertensive effect of beta-blocking drugs in low and normal-high renin hypertension.

The treatment response to beta-adrenoceptor blocking drugs was compared in two groups of patients with primary (essential) hypertension and different renin levels. Each group consisted of 25 patients and was equally distributed regarding age, severity and stage of hypertension. In the first group (group 1), the mean upright plasma renin activity was 0.8 ng ml-1h-1 (range 0.3 to 1.5) and the patients were considered to have low renin hypertension. In the other group (group 2) the patients had a mean plasma renin activity of 2.1 ng ml-1h-1 (range 1.1 to 5.1) and were considered to have normal to high renin hypertension. In both groups the patients were initially treated with beta-blocking drugs; in group 1 with a beta-blocker corresponding to an average dose of 311 mg propranolol a day for at least eight weeks and in group 2 with propranolol 320 mg a day in a fixed dose for eight weeks. The hypotensive response differed significantly between the two groups (p less than 0.001). In group 1 the pretreatment blood pressure was 197/117 mm Hg supine and 198/120 mm Hg standing. During treatment blood pressure decreased only 5/3 mm Hg supine and 9/5 mm Hg standing. The pretreatment blood pressure in group 2 was 187/114 mm Hg supine and 186/117 mm Hg standing. Beta-blocking therapy reduced blood pressure 36/23 and 34/18 mm Hg, respectively (both p less than 0.001). Pulse rates fell significantly in the two groups, both in the lying and standing positions. In 17 patients with low renin hypertension (group 1), a volume-depleting drug was added (spironolactone, 14 patients; thiazides, 3 patients) and this achieved a marked fall in blood pressure levels of 38/16 mm Hg supine and 37/19 mm Hg standing (both p less than 0.001). These results suggest the following: (1) Most patients with normal to high plasma renin activity respond well to moderate doses of propranolol. (2) Propranolol given in the same doses is almost without antihypertensive effect in patients with low renin hypertension. (3) A volume factor may be operating in patients with low renin hypertension since a hypotensive effect is demonstrated after the addition of volume-depleting drugs. (4) Determination of plasma renin activity with adequate methods can predict the treatment response to hypotensive agents.     

Aldosterone Responsiveness to Angiotensin II After Sodium Restriction in Subjects With Low Renin Essential Hypertension

Plasma aldosterone (PA) responses to sodium restriction (25 mEq sodium/day for 4 days) and to graded angiotensin II (All) infusions (2,4 and 8 ng/kg/min each for 30 min) during a low sodium intake were studied in 14 subjects with low renin essential hypertension (LREH) versus 16 normotensive subjects. The PA response to sodium restriction in relation to changes in plasma renin activity (PRA) was estimated by the ratio of PA increment to PRA increment after sodium restriction (ΔPA/ΔPRA). In 8 of 14 LREH subjects, whose ΔPA/ΔPRA ratios were normal, the PA responses to the graded All doses were similar to those in the normotensive subjects. However, in the remaining 6 LREH subjects whose ΔPA/ΔPRA ratios were high the PA responses to the graded All doses were greater. Apparently some LREH subjects, whose ΔPA/ΔPRA ratios after sodium restriction were high, have an abnormally enhanced aldosterone responsiveness to All under the condition of low sodium intake.     

Correction of altered noradrenaline reactivity in essential hypertension by indapamide.

Fourteen patients with untreated mild to moderate essential hypertension had on average an abnormally high cardiovascular reactivity to exogenous noradrenaline and angiotension II, while plasma noradrenaline, renin activity, exchangeable body sodium, and blood volume were normal. Treatment with a low dose of indapamide (2.5 mg/day) for six weeks decreased blood pressure by 10% in these hypertensive patients but not in 13 normal control subjects. Plasma or blood volume and exchangeable sodium were not changed significantly; nevertheless, the latter, and body weight, tended to be decreased slightly. Though a mild reduction in extracellular sodium in both normal and hypertensive subjects appears possible, it may not per se fully explain indapamide's blood pressure-lowering effect in essential hypertension. Indapamide induced a mild decrease in angiotensin II pressor responsiveness in normal or hypertensive subjects, but a possible depressor influence from this change was probably antagonised by a concomitant pronounced increase in plasma renin activity. In hypertensive patients, the abnormally high noradrenaline reactivity was corrected by indapamide without an accompanying increase in endogenous plasma noradrenaline levels. Indapamide-induced changes in blood pressure correlated with those in noradrenaline pressor dose. It was concluded, therefore, that indapamide may decrease blood pressure in essential hypertension at least in part by lowering an abnormally high cardiovascular noradrenaline reactivity without causing an equivalent increase in adrenergic nervous activity.     

Supine and Standing Plasma Catecholamines in Essential Hypertensive Patients with Different Renin Levels

In this study we measured plasma renin activity (PRA), plasma norepinephrine (NE) and epinephrine (E), heart rate (HR) and blood pressure (BP) in 89 supine (sup) essential hypertensive patients (pts), WHO I–II, after 3–5 days of fixed normal sodium and potassium intake; the same measurements were repeated after 30′ of active standing (stand) in 44/89 pts. In the whole population NE was directly related to PRA, both in sup and in stand position (p < 0.01). NE was above the upper limits of normotensive controls in 2/34 (6%) pts with low PRA, in 6/40 (17%) pts with normal PRA and in 6/15 (40%) pts with high PRA. In respect to normal PRA pts, HR was significantly lower in low PRA pts and higher in high PRA pts, both in sup and in stand position (p < 0.05). Sup and stand NE and E were similar in low and normal PRA pts, while they were significantly higher in high PRA pts (p < 0.05). These results suggest an increased adrenergic tone at least in some high PRA pts, and blunted responsiveness of renal and cardiac beta adrenergic receptors to adrenergic stimuli in low PRA pts     

Effects of angiotensin-converting enzyme inhibition on blood pressure and plasma renin activity in essential hypertension

Oral converting enzyme inhibitor SQ14225 was administered in 11 patients with essential hypertension, in order to investigate the role of the renin-angiotensin system in the regulation of blood pressure in essential hypertension. In the sodium-repleted state (150 mEq sodium intake for 6 days) in 11 patients, converting enzyme inhibitor decreased the average mean blood pressure from 113 +/- 2 to 106 +/- 2 mm Hg (p less than 0.001). Plasma renin activity increased with sodium depletion (30 mEq sodium intake for 3 days after furosemide treatment) from 1.26 +/- 0.07 to 3.26 +/- 0.48 ng/ml/hr (p less than 0.001). In the sodium-depleted state the hypotensive effect of SQ 14225 was more pronounced (mean blood pressure 108 +/- 2 to 93 +/- 3 mm Hg). The decrease in mean blood pressure caused by the inhibitor correlated to the basal plasma renin activity (r = -0.53, p less than 0.02, n = 22 measurements). The results indicate that the renin-angiotensin system participates in the regulation of blood pressure in essential hypertension, even in the sodium-repleted state. This role of the renin-angiotensin system in blood pressure regulation becomes more crucial during sodium depletion.     

Relation of renin status to neurogenic vascular resistance in borderline hypertension.

The relation of renin-angiotensin status to general hemodynamics and to neurogenic vascular resistance was studied in patients with border-line hypertension. Plasma renin activity during standing was referred to a standard renin-urinary sodium nomogram derived from 18 normal subjects. Among 22 patients with borderline hypertension the renin level was high in 8, low in 4 and within normal limits in the remaining 10. In patients with borderline hypertension and high or normal levels of plasma renin activity, the blood pressure elevation was due to increased total peripheral vascular resistance. In contrast, in patients with low renin borderline hypertension, total peripheral resistance was not significantly elevated; the blood pressure elevation reflected a cardiac index 12 percent higher than that in normal subjects. The neurogenic contribution to total peripheral vascular resistance was assessed by studying the effects of alpha adrenergic blockade with phentolamine, after prior autonomic blockade of the heart with atropine (0.04 mg/kg body weight) and propranolol (0.2 mg/kg). Phentolamine (15 mg) produced an immediate reduction in total peripheral resistance of 12.0 +/- 6.7 percent in patients with high renin borderline hypertension (P less than 0.01) but no change in normal subjects or those with borderline hypertension and normal or low renin levels. Normalization of the blood pressure followed "total" autonomic blockade with atropine, propranolol or phentolamine only in patients with high renin borderline hypertension. It is concluded from these preliminary data that in high renin borderline hypertension the blood pressure elevation is sustained by neurogenic mechanisms. The elevated renin level in these patients is probably an expression of increased sympathetic nervous activity. Although the elevated plasma renin level may possibly be contributing to the generation of higher sympathetic tone, or data do not support a direct role of circulating angiotensin in the maintenance of the elevated vascular resistance.     

Relation between dopamine secretion and saltsensitivity in essential hypertension

The study was designed to explore the mechanism of dopamine secretion related to blood pressure in patients with essential hypertension. The 19 patients with essential hypertension were administered to first 153 mEq of sodium and 70 mEq of potassium diet, next 51 mEq of sodium and finally 340 mEq of sodium for every one week. The patients whose mean blood pressure elevated 10 mmHg or more on the high-sodium loading and depleted 10 mmHg or more on the low-sodium loading were classified as A-, and depleted 10 mmHg or more on the high-sodium loading and elevated 10 mmHg or more on the low-sodium loading as B- and the other patients as C-group. The hypertensive patients were also classified to low- (below 1.0 ng/ml/h), normal- (from 1.0 to 6.0 ng/ml/h) and high- (above 6.0 ng/ml/h) renin groups from the results of plasma renin activity (PRA) obtained after an intravenous injection of furosemide (1 mg/kg) followed by 2-hour ambulation. PRA, plasma aldosterone concentration (PAC), plasma epinephrine concentration (PE), plasma norepinephrine concentration (PNE), plasma dopamine concentration (PDC), circulating plasma volume, body weight, hematocrit and pulse rate were measured at 8 a.m. after sodium loading for 8-days. The patients with essential hypertension were classified into 6 of A- and 2 of B- and 11 of C-groups with the maneuver of sodium loading. The A-group contained 5 patients with low-renin. The circulating plasma volume was relatively large (44.7 +/- 4.8 ml/kg) and markedly increased on the high-sodium loading in 6 patients of A-group. The increment of body weight was higher in A-group than the other groups on the high-sodium loading. In the 2 patients of B-group, hematocrit and pulse rate increased on the low-sodium and decreased on the high-sodium loading, and the variability were larger than the other groups. In the A-group, PRA was significantly low (0.5 +/- 0.4 ng/ml/h) and increased on the low-sodium loading and decreased on the high-sodium loading, and the variability of PRA was lesser than the other groups. In the A-group, PAC was within normal range (5.4 +/- 2.8 ng/dl) and the variation of PAC paralleled with the change of PRA, but the variability of PAC was remarkably low. PE and PNE were unchanged in the A- and the C-groups, but the significant high values were observed in the B-group on the high-sodium loading.     

Vascular responses to ouabain and norepinephrine in low and normal renin hypertension

A circulating Na+, K+-ATPase inhibitor may cause arterial hypertension in patients with suppressed plasma renin activity, either directly or by sensitizing peripheral vessels to alpha-adrenergic stimulation. This hypothesis was tested by evaluating forearm arteriolar (plethysmographic technique) response to exogenous alpha-adrenergic stimulation by a 2-minute intra-arterial infusion of norepinephrine (0.1 microgram/dl tissue per minute) and to Na+, K+-ATPase inhibition by sequential 20-minute intra-arterial infusions of ouabain (0.36 and 0.72 microgram/dl tissue per minute). Two groups of hypertensive subjects with suppressed plasma renin activity, either essential or secondary to aldosterone excess, were compared with age-matched and sex-matched hypertensive subjects with normal plasma renin activity (n = 7 per group). No significant differences in forearm vascular response to norepinephrine were found among the three groups. Ouabain caused a highly significant, dose-related increment in forearm vascular resistance that was not accompanied by changes in the contralateral limb or systemic blood pressure. No significant interindividual differences in vascular responsiveness to ouabain were found. The individual increments in forearm vascular resistance during ouabain administration were unrelated to basal values or to plasma aldosterone, norepinephrine, or potassium concentrations. These data are not consistent with the hypothesis that suppressed basal Na+, K+-ATPase activity is primarily a characteristic of hypertensive patients with unresponsive plasma renin activity. Overall, these results cast doubts on the possibility of linking the development of human low renin hypertension to an endogenous Na+, K+-ATPase inhibitor.     

Relationship of plasma renin activity and aldosterone levels with hemodynamic functions in essential hypertension.

Correlates of plasma renin activity and plasma aldosterone levels with hemodynamic functions were studied in 47 male patients with untreated, permanent essential hypertension. All subjects had a normal creatinine clearance and received a diet of 110 mEq/day of sodium. Supine plasma renin activity was directly correlated with cardiac index (P less than.01) and cardiopulmonary blood volume (P=.01).Percentage changes in plasma renin activity and total peripheral resistance in response to upright position were positively correlated (P less than.001). Supine plasma aldosterone level was directly correlated with stroke index (P less than .001) and negatively correlated with hear rate (P less than .05). No significant correlation of aldosterone level was observed with the other measurements, including plasma renin activity. The study points to the neural sympathetic control of plasma renin activity in essential hypertension and suggests the existence of some interrelationships between aldosterone level and cardiac performance.     

Abnormal norepinephrine and aldosterone responses to upright posture in nonmodulating hypertension.

The subgroup of patients with nonmodulating hypertension demonstrates a number of abnormalities of the renin-angiotensin-aldosterone axis. We previously identified abnormalities in plasma and urinary dopamine in nonmodulators and posited that this may be in part due to a generalized defect in sympathetic nervous system activity. In the present study we assessed the state of activation of the renin-angiotensin system and the sympathetic nervous system in normal subjects and patients with modulating, nonmodulating, and low renin essential hypertension during sodium depletion and change from supine to upright posture. Levels of plasma norepinephrine were higher in non-modulators during the posture study (P < 0.05). PRA rose with upright posture in all groups, but low renin subjects had a blunted response. Nonmodulators and low renin subjects had lower aldosterone levels both supine (P< 0.05) and upright (P< 0.01). However, the aldosterone/PRA increment ratio was increased in low renin subjects (P< 0.01), whereas it was decreased in nonmodulators. Twenty-four-hour urine collections for catecholamine determinations were obtained in a subgroup of the subjects, with nonmodulators showing higher levels of norepinephrine excretion which approached significance (P = 0.08). In vitro experiments using rat and human adrenal glomerulosa cells showed that norepinephrine does not affect aldosterone secretion per se. These observations extend the series of abnormalities observed in nonmodulating hypertension. However, it is likely that the alterations in norepinephrine levels during sodium depetion and upright posture are a secondary event and not linked to the altered aldosterone production in these patients.     

Effect of pressor agents on blood pressure, plasma renin activity and plasma aldosterone concentration in essential hypertension.

The responses of blood pressure, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) to infusion of either angiotensin II (10 ng/Kg/min) or norepinephrine (100 ng/Kg/min) were observed in 25 patients with essential hypertension. The difference in modes of response between low renin essential hypertension and normal or high renin essential hypertension was analyzed. For comparison, 5 patients with Conn's syndrome, 4 with renovascular hypertension, and 5 normotensive subjects were also studied. Following infusion of antiotensin II the changes in diastolic blood pressure (DBP) were +24+/-3.0 mmHg in low renin essential hypertension and +25+/-3.1 mmHg in normal or high renin essential hypertension in PRA -0.28+/-0.06 ng/ml/h in low renin essential hypertension and -0.69+/-0.02 mg/ml/h in order and in PAC +3.7+/-1.4 and +7.6+/-1.8 ng/100 ml respectively. There was a significant difference in magnitude of response in PRA between the 2 groups of essential hypertension (p less than 0.05). Norepinephrine induced rise in DBP with decreases both in PRA and PAC. The mean changes in DPB were +6+/-1.4 mmHg in low renin essential hypertension and +16+/-2.2 mmHg in another and the pressor response in the later was significantly greater (p less than 0.01). The changes in PRA were -0.14+/-0.07 ng/ml/h in low renin essential hypertension and -0.67+/-0.26 ng/ml/h in normal or high renin essential hypertension, and in PAC -4.9+/-1.3 and -3.3+/-1.9 ng/100 ml respectively. The greater fall in PRA in normal or high renin essential hypertension was observed but the difference between the 2 groups of essential hypertension was not significant. The changes in PAC did not parallel the changes in PRA. Angiotensin II indcued essentially similar effects on blood pressure in both groups but the greater feedback inhibition of PRA was produced by this peptide in normal or high renin essential hypertension than in low renin essential hypertension. Norepinephrine induced significantly greater pressor effect in normal or high renin essential hypertension. The adopted dose of norepinephrine suppressed both PRA and PAC and a tendency to the greater fall in PRA was observed in normal or high renin essential hypertension. There was no difference in responses of PAC to both agents between the 2 groups of essential hypertension.     

Contrasting effects of hypoglycemia on plasma renin activity and cyclic adenosine 3',5'-monophosphate (cyclic AMP) in low renin and normal renin essential hypertension.

Insulin-induced hypoglycemia previously has been shown to provoke a beta-adrenergic response that normally results in an increase in plasma renin activity (PRA). In our study, hypoglycemia induced definite increases in PRA in a group of five patients with normal renin essential hypertension but failed to do so in a group of six patients with low renin essential hypertension. In both groups, plasma cyclic adenosine 3',5'-monophosphate (cyclic AMP; cAMP) increased more than 2-fold during hypoglycemia, but the response in the low renin group was significantly less than that previously observed in normal subjects under the same conditions. Plasma cortisol increased to an equal extent in both groups of hypertensive patients during hypoglycemia. Infusion of the phosphodiesterase inhibitor, theophylline, resulted in definite increases of PRA in patients with normal renin hypertension but not in patients with low renin hypertension. Because changes in the level of plasma cAMP during hypoglycemia have been thought to reflect adrenal catecholamine release, our finding of a blunted increase in plasma cAMP during hypoglycemia in patients with low renin hypertension may suggest that there is a generalized alteration in adrenergic responsiveness in this condition.     

Captopril modifies the hemodynamic and neuroendocrine responses to sodium nitroprusside in hypertensive patients

To determine if clinically effective doses of the antihypertensive agent captopril affected the neuronal release of norepinephrine or baroreflex sensitivity, changes in plasma norepinephrine concentration and heart rate were related to the changes in mean arterial pressure seen during the intravenous infusion of stepwise incremental doses of sodium nitroprusside before and during captopril treatment in eight hypertensive men with normal or low plasma renin activity. At all times, significant linear correlations were found between the decrease in mean arterial pressure and the dose of sodium nitroprusside, the increase in heart rate and the decrease in mean arterial pressure, and the increase in plasma norepinephrine concentration and the decrease in mean arterial pressure. When the subjects were treated with captopril (25 mg t.i.d.) for 2 to 4 weeks, supine mean arterial pressure decreased from 130 to 114 mm Hg (-12%; p less than 0.05), heart rate did not change, supine and upright plasma renin activity increased, while supine plasma norepinephrine and epinephrine concentration decreased slightly. Therapy with captopril (25 mg t.i.d.) increased baroreflex sensitivity, as assessed by the slope of the regression line relating the increase in heart rate to the decrease in mean arterial pressure, and increased the responsiveness of the sympathetic nervous system, as assessed by the slope of the regression line relating the increase in plasma norepinephrine concentration to the decrease in mean arterial pressure. These increases were accompanied by a decrease in the slope of the regression line relating the decrease in mean arterial pressure to the dose of sodium nitroprusside and thus were associated with a decreased sensitivity to the vasodepressor effects of sodium nitroprusside.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of diltiazem on hemodynamics, plasma catecholamine and renin activity during exercise in hypertension]

The effects of diltiazem on hemodynamics, plasma catecholamine and plasma renin activity were studied during treadmill exercise test in 9 cases with moderate essential hypertension. Diltiazem of 120 mg/day was orally administered for 4 weeks. At maximum exercise, significant decrease in systolic blood pressure (-32 mmHg), heart rate (-16/min), pressure-rate product (-7,883 mmHg/min), plasma norepinephrine (-195 ng/L) and plasma epinephrine (-11 ng/L) were observed; while, diastolic blood pressure, ST depression and plasma renin activity showed no significant change. Also, a significant correlation between systolic blood pressure and plasma norepinephrine (r = 0.57, p < 0.001), especially after diltiazem therapy (r = 0.68, p < 0.001), was observed. These findings indicated that diltiazem can reduce the secretion of catecholamine from the sympathetic nerves during exercise in patients with essential hypertension.