Toru Naka

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.

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.

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 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