Anna Maruyama

The Seasonal Variation of Blood Pressure in Patients with Essential Hypertension

We examined the role of dietary electrolytes and humoral factors in causing seasonal changes in blood pressure. Normal subjects had no seasonal difference in blood pressure, although urinary sodium and norepinephrine were significantly higher in winter than in summer. In patients with essential hypertension blood pressure, urinary sodium and norepinephrine excretion and plasma norepinephrine concentration were significantly higher in winter. Plasma renin activity, plasma and urinary aldosterone and urinary kallikrein excretion were not significantly different between the two seasons in both normal subjects and hypertensive patients. In conclusions, the blood pressure of patients with essential hypertension has a seasonal variation with higher pressures in the winter than in the summer. Increased sympathetic nervous activity and an increased load of sodium presented to the kidney for excretion may be contributing factors in the rise in blood pressure in winter in patients with essential hypertension.

Hormonal responses to long‐term converting enzyme inhibition in hypertensive patients

Captopril was given alone and in combination with diuretics to 49 patients with hypertension for 1 to 12 mo. Within 2 mo blood pressure reduction correlated with pretreatment plasma renin activity and response to the infusion of angiotensin II antagonist, but these effects were not present at 4 mo. Plasma and urinary aldosterone were suppressed but serum converting enzyme activity, plasma bradykinin, kallikrein, and prostaglandins (E and F) were in the normal range throughout the study period. Indomethacin (150 mg/day) for 1 wk abolished the hypotensive effect of captopril. Despite sustained reduction of blood pressure, plasma catecholamines were not elevated and urinary catecholamines were suppressed in patients on captopril alone. It is concluded that another mechanism, such as enhancement of renal or local kinin‐prostaglandin system, as well as suppression of the renin‐angiotensin‐aldosterone system may be involved in the long‐term efficacy of captopril. Sympathetic activity may also be depressed and contribute to the hypotensive effect.

Effect of Age on Active and Inactive Plasma Renin in Normal Subjects and in Patients with Essential Hypertension

The effect of age on the levels of active and trypsin‐activatable inactive plasma renin was examined in 41 normal subjects and 54 patients with essential hypertension, during recumbency and after stimulation with furosemide and ambulation. Active renin levels in supine subjects and patients decreased with age. Inactive renin levels did not change with age in normal subjects, whereas in hypertensive patients they decreased with age. Following stimulation with furosemide and ambulation, the levels of active renin increased but the responsiveness to stimulus decreased with age in both groups. In contrast, inactive renin levels slightly increased after furosemide administration and ambulation, resulting in an increased proportion of active to total renin. These data show that an acute stimulation with furosemide and ambulation affects mainly the active form of plasma renin, and the effect of age on inactive plasma renin in normal subjects may be different from that in patients with essential hypertension.

A case of normoreninemic, normotensive primary aldosteronism associated with essential hypertension and nephrocalcinosis.

A 36-year-old female case of normotensive normoreninemic primary aldosteronism with persistent hypokalemia and nephrocalcinosis is reported. She was referred to us for episodes of sudden muscle weakness during 8 years prior to admission. On the first day of admission, her blood pressure was 174/104 mmHg. On the second day of admission blood pressure normalized to 120/80 mmHg. Both of her parents were hypertensive. Arterial blood gas analysis showed metabolic alkalosis. Except an impaired urine concentration ability, renal functions were normal. Intravenous pyelogram showed numerous granular calcifications. Basal plasma renin activity was 1.0 approximately 1.5 ng/ml/hr and increased by sodium depletion. Plasma aldosterone concentration was 70 approximately 80 ng/dl and did not respond to various stimulations. Blood pressure was dependent on sodium balance. It fell on salt restriction and rose on salt loading. Blood pressure responses to vasoactive hormones were normal. Circulating plasma volume was within normal range. After removal of an adrenal adenoma, there was mild fall of blood pressure, serum potassium returned to normal level and plasma renin activity increased slightly. Histologically, there was renal tubular calcifications, and juxtaglomerular apparatus was normal. Blood pressure was elevated to 160/100 mmHg when patient was followed at out-patient clinic after discharge. We concluded that she had essential hypertension associated with primary aldosteronism. Although sodium loss and an increase in urinary kallikrein were found, they did not seem to be the cause of normoreninemic normotensive state of this patient, and the pathogenesis remains to be elucidated.

Long‐term effects of captopril in hypertension

Captopril was given for treatment of hypertension alone or in combination with diuretics to 32 patients for 1‐ to 4‐mo periods. The decrement of mean blood pressure after 1 and 2 mo correlated with pretreatment plasma renin activity (PRA) and the response of blood pressure to infusion of an angiotensin II antagonist. These correlations were no longer apparent after 4 mo of treatment. When subjects with a decrement of mean blood pressure that exceeded 13 mm Hg were compared with nonresponders, responders not only had higher control PRA and higher PRA at 1 mo of treatment, but also had decreased plasma aldosterone levels, decreased urinary aldosterone excretion, and increased serum postassium levels that persisted over the 4 mo of observation. The reduction of plasma aldosterone correlated with the fall of mean blood pressure. Urinary kallikrein, catecholamines, electrolytes, and endogenous creatinine clearance did not change in response to treatment. These findings indicate that the antihypertensive activity of captopril on long‐term administration probably depends in part on the blockade of angiotensin II, but other mechanisms cannot be excluded.

Sodium depletion and blood pressure response to 1‐sarcosine, 8‐isoleucine angiotensin II in hypertension

The relation of sodium balance to the blood pressure response to 1‐sarcosine, 8‐isoleucine angiotensin II ([Sar1, Ile8]AII) was evaluated in patients with hypertension of various causes. Tests with [Sar1, Ile8]AII were made under the following three conditions: (1) unrestricted diet and no diuretic pretreatment, (2) unrestricted diet and 40 mg furosemide intravenously 2 hr before the test, and (3) mild salt restriction (5 gm NaCl/day) and 80 mg furosemide orally for 3 days before the test. Among patients with renovascular or malignant hypertension, 5 of 14 cases (36%) in condition 1, 3 of 6 cases (50%) in condition 2, and 7 of 7 cases (100%) in condition 3, there was a reduction of more than 10 mm Hg in the mean blood pressure. The pressor responses in essential hypertension and in primary aldosteronism were reduced by sodium depletion. All patients with pressor responses of over + 10 mm Hg in condition 3 were patients with primary aldosteronism. These results indicate that before the [Sar1, Ile8]AII test sodium depletion is useful not only for preventing an excessive pressor response in low reninemic patients but also for increasing the specificity of the test in the evaluation of renin‐dependent hypertension. Angiotensin II‐inhibiting analogues are useful in the detection of abnormally high or abnormally low renin levels.

Is normoreninemic essential hypertension caused by disordered central dopaminergic regulation

Some investigators have reported that plasma prolactin levels are elevated in hypertensive men and that both their hyperprolactinemia and hypertension were controlled by bromocriptine, a dopamine agonist. They concluded that reduced central dopaminergic activity may be a factor in maintaining essential hypertension. We examined the serum prolactin and thyrotropin (TSH) responses to thyrotropin releasing hormone (TRH), metoclopramide (a dopamine antagonist) and bromocriptine in 10 normal and 10 hypertensive normoreninemic men. TRH caused significant increase of both prolactin and TSH and metoclopramide caused significant increase of prolactin in both normals and hypertensives. Bromocriptine suppressed prolactin and TSH significantly in both groups. There were no significant differences in prolactin and TSH levels between the normal and hypertensive groups before or during the tests. These results provide no support for the hypothesis that alterations in the activity of central dopaminergic neurons are involved in the maintenance of the elevated blood pressure of normoreninemic men with essential hypertension.

Comparison of the biological effects of two angiotensin II analogues in hypertensive patients with sodium depletion

Abstract The effects on blood pressure (BP), plasma aldosterone concentration (PAC) and plasma renin activity (PRA) of two angiotensin II analogues (AII A), i.e., 1-sarcosine, 8-isoleucine angiotensin II (Sar 1 , I1e 8 -AII) and 1-sarcosine, 8-alanine angiotensin II (Sar 1 , Ala 8 -AII), were investigated in patients with hypertension with various etiologies on sodium depletion. The changes of BP, PAC and PRA on infusion of Sar 1 , Ile 8 -AII and Sar 1 , Ala 8 -AII were very similar. With both compounds, there were significant inverse correlations between the pre-infusion PRA and the changes in BP and PAC, and a significant positive correlation between the pre-infusion PRA and change in PRA. The slopes of the regression lines for the correlations of changes in BP, PAC and PRA, plotted as functions of the pre-infusion PRA for Sar 1 , Ile 8 -AII and Sar 1 , Ala 8 -AII were not statistically different. In clinical investigations, the two compounds seemed equally useful for detecting renin-dependency in hypertension.

DECREASED BLOOD PRESSURE IN RESPONSE TO AN ANGIOTENSIN II ANTAGONIST IN ADDISON'S DISEASE

The synthetic angiotensin II antagonist, 1‐sarcosine, 8‐isoleucine angiotensin II was infused in two patients with untreated Addisons disease. Blood pressure decreased following infusion of this angiotensin II antagonist. Re‐infusion of the antagonist after cortisol replacement therapy for one month caused a slight increase in blood pressure. Addisons disease is one of the conditions in which the renin‐angiotensin system is involved in the maintenance of blood pressure.

[Comparison of blood pressure responses to captopril, an orally active converting enzyme inhibitor, in rats with various forms of experimental hypertension (author's transl)].

Captopril, a potent and orally active converting enzyme inhibitor is believed to exert its hypotensive effect largely through the inhibition of the renin-angiotensin system (RAS) . In order to examine the renin dependency of blood pressure (BP) in normal rats and rats with two-kidney Goldblatt hypertension (2KGH), spontaneous hypertension (SH) and DOCA-salt hypertension (DSH), we examined the responses of these animals to prolonged administration of captopril. Two types of studies were done on the hypertensive animals: one was performed in the chronic phase when hypertension was established (chronic phase study), and the other was started in the prehypertensive phase (prevention study). Normal rats were studied with and without captopril treatment. 2KGH rats and SHR in the chronic