Komei Saito

The great Hanshin-Awaji earthquake aggravates blood pressure control in treated hypertensive patients

A major earthquake (Hanshin-Awaji earthquake) struck Kobe on January 17, 1995. We had a unique opportunity to study the effect of tremendous psychological stress on blood pressure control in 221 hypertensive patients receiving antihypertensive medication. During the 4 weeks after earthquake, on average, the mean blood pressure increased significantly for both 105 patients who were exposed (living in the area of the very severe earthquake) and 116 patients who were not exposed (living in the surrounding area) (+4.2 +/- 1.0 mm Hg, P < .001, and +/- 2.4 +/- 0.7 mm Hg, P < .005, respectively). In the exposed group, the increase in mean blood pressure peaked in the first week (+6.7 +/- 1.6 mm Hg, P < .001), declined thereafter, and returned to the baseline within 6 weeks after the disaster. The earthquake related blood pressure elevation was, however, significantly attenuated (P < .02) in patients receiving beta-blockers compared with those receiving other drugs. The results indicate that acute psychological stress associated with a sudden natural disaster causes blood pressure elevation in treated hypertensive patients, and suggest the beneficial effect of beta-blockers on such a stress-associated high blood pressure.

Effect of oral calcium on blood pressure response in salt-loaded borderline hypertensive patients.

To clarify the mechanism of the antihypertensive effect of oral calcium loading, we studied the effect of low versus high calcium intake on salt-induced blood pressure elevations in patients with borderline hypertension. After a 7-day period of dietary salt restriction (50 meq/day), 27 patients were placed on a high salt (300 meq/day), low calcium (250 mg/day) diet for 7 days; 14 of these patients were given 2,160 mg/day of supplementary calcium (Ca group), and 13 patients were given placebo (non-Ca group). With a high salt intake, the percent increase in mean blood pressure was smaller in the Ca group than in the non-Ca group (+2.85 +/- 1.22% vs. +8.63 +/- 1.66%, respectively, p less than 0.01). The Ca group showed a smaller weight gain (p less than 0.05) and a greater urinary excretion of sodium (p less than 0.005) than the non-Ca group. In the Ca group, but not in the non-Ca group, high salt intake resulted in an increase in intraerythrocyte magnesium content (p less than 0.01), which was correlated inversely with the salt-induced changes in mean blood pressure (r = -0.54, p less than 0.05). While the increase in cellular magnesium was greater in the Ca group, the changes in red blood cell sodium and sodium/potassium ratio were not different between the two groups. The results suggest that oral calcium supplementation may prevent a rise in blood pressure in patients on a high salt, low calcium diet by attenuating the sodium retention.(ABSTRACT TRUNCATED AT 250 WORDS)

Nitric Oxide Synthase Isoform Activities in Kidney of Dahl Salt-Sensitive Rats

An abnormal L-arginine-nitric oxide axis has been suggested to be relevant to the genesis of salt-sensitive hypertension. In the present study we investigated the activities of three isoforms of nitric oxide synthase (NOS) in the kidney of Dahl salt-sensitive and salt-resistant rats. Five-week-old Dahl Iwai salt-sensitive (n = 9) and salt-resistant (n = 10) rats were maintained on a high salt diet (4% sodium chloride) for 4 weeks. We measured calcium-dependent and calcium-independent NOS activities in each particulate and soluble fraction of kidney by conversion of L-[3H]arginine to L-[3H]citrulline. Systolic blood pressure was elevated significantly (P < .001) in salt-sensitive but not salt-resistant rats. Calcium-dependent NOS activity in the soluble fraction was significantly lower in salt-sensitive rats than in salt-resistant rats (25.8 +/- 9.0 versus 48.2 +/- 19.2 disintegrations per microgram protein, respectively; P < .01). There were no differences in calcium-dependent NOS activity in the particulate fraction and calcium-independent NOS activity in the soluble fraction between groups. Renal norepinephrine content was lower in salt-sensitive rats than in salt-resistant rats (P < .05) and was positively correlated with calcium-dependent NOS activity in the soluble fraction (P < .01). Although no differences in endothelial and inducible-type NOS activity were observed a significant reduction in calcium-dependent NOS activity in the soluble fraction of the kidney of salt-sensitive rats suggests that the decreased neural-type NOS activity may in part be involved in the mechanism of salt-sensitive hypertension, possibly through alterations in renal sympathetic nervous activity and sodium handling.

Deep negative T waves and abnormal cardiac sympathetic image (123I-MIBG) after the Great Hanshin Earthquake of 1995.

The authors report the increased incidence of patients with deep negative T waves without Q wave after the Great Hanshin Earthquake of 1995. Subjects underwent cardiac metaiodobenzyl guanidine (123I-MIBG) imaging, 201Tl scintigraphy, and coronary angiography. Among 2,756 inpatients of the preceding 5-year period, 33 (1.2%) showed the deep negative T waves, whereas 6 of 94 (6.4%; P < 0.001) showed it after the earthquake. Four of six patients had an episode of chest pain. Cardiac metaiodobenzyl guanidine imaging revealed the extent defects in all six patients despite a minimal change of 201Tl image. In addition, cardiac metaiodobenzyl guanidine imaging washout rate was hastened not only in the defect area but also in the nondefect area, which suggested augmented sympathetic activation. Natural disasters can affect the frequency of deep negative T waves, which relate abnormal cardiac sympathetic imaging.

Expression of Fos-like immunoreactivity by yohimbine and clonidine in the rat brain

To elucidate the role of alpha 2-adrenoceptors in transcriptional control in the rat brain, we localized the Fos-like immunoreactivity (Fos-LI) induced by alpha 2-adrenoceptor agonists and by an antagonist. Injections of yohimbine (5 mg/kg, i.p.) into rats led to the induction of Fos-LI in areas with a dense alpha 2-adrenoceptor binding such as the locus coeruleus, the bed nucleus of stria terminalis, the central nucleus of amygdaloid complex, the paraventricular nucleus, the nucleus tractus solitarius, and ventrolateral medulla oblongata. Clonidine (500 micrograms/kg, i.p.) suppressed the Fos expression by yohimbine in these nuclei, and clonidine (100 micrograms/kg, i.p.) or guanabenz (4 mg/kg, i.p.) induced Fos-LI in oxytocin neurons in the paraventricular and supraoptic nuclei in the hypothalamus. Thus, the alpha 2-adrenoceptor is involved in transcriptional control via Fos expression in neurons related to autonomic and other functions.

A Circulating Na+-K+ATPase Inhibitor, Erythrocyte Sodium Transport and Hypertension in Patients with Chronic Renal Failure

The level of circulating Na+-K+ATPase inhibitor (% inhibition), erythrocyte ouabain-sensitive 22Na+ efflux rate constant (Kos) and erythrocyte sodium content (RBC Na) were measured in 11 undialysed patients with chronic renal failure, 16 patients on chronic hemodialysis and 16 age-matched normotensive healthy controls. In uremics, % inhibition was significantly higher than that in the controls (p less than 0.001). There were significant correlations between % inhibition and both mean blood pressure (r = 0.74, p less than 0.001) and Kos (r = -0.47, p less than 0.005) for all the groups combined. Hypertensive uremics showed significantly higher % inhibition, lower Kos and higher RBC Na compared with normotensive ones. These data suggest that the elevated level of circulating Na+-K+ ATPase inhibitor may, at least in part, account for the pathogenesis of hypertension in patients with chronic renal failure.

Effects of Alcohol Moderation on Blood Pressure and Intracellular Cations in Mild Essential Hypertension

It is known that moderation of alcohol intake reduces blood pressure, although the exact mechanism has not yet been established. To clarify the hypotensive mechanism of alcohol reduction, we evaluated the change in cellular magnesium and sodium metabolism during alcohol reduction in mild hypertensive patients. We measured intraerythrocyte sodium and magnesium, intraplatelet free magnesium concentrations, and erythrocyte ouabain-sensitive 22Na efflux rate constant (Kos) in 17 mild essential hypertensive patients regularly consuming more than 40 g/day of alcohol, before and after 4 weeks of alcohol reduction, and 12 age-matched nondrinking hypertensives. Intraerythrocyte magnesium (P < .01) and intraplatelet free magnesium (P < .05) concentrations were significantly lower in drinkers than in nondrinkers. In drinkers, advice to reduce alcohol intake for 4 weeks resulted in a reduction in self-reported alcohol consumption from 461.7 to 71.6 g/week, a significant fall in both supine systolic blood pressure (136.3 +/- 10.8 to 130.8 +/- 11.3 mm Hg, P < .001) and supine diastolic blood pressure (85.1 +/- 8.6 to 82.6 +/- 8.7 mm Hg, P < .05). The fall in mean blood pressure correlated positively with the reduction in weekly alcohol consumption. Intraerythrocyte magnesium and Kos were increased (P < .05, P < .01, respectively), while intraerythrocyte sodium was decreased (P < .01). The increase in intraerythrocyte magnesium correlated negatively with the fall in mean blood pressure and positively with the increase in Kos, which correlated negatively with the decrease in intraerythrocyte sodium.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Supplementation Attenuates an Enhanced Platelet Function in Salt-Loaded Mildly Hypertensive Patients

We designed this study to evaluate the effect of low versus high calcium intake on platelet function in salt-loaded patients with mild hypertension. After a 7-day period of dietary salt restriction, 19 patients were placed on a high salt (300 mmol/d), low calcium (6.25 mmol/d) diet for 7 days; 10 of these patients were given 54 mmol/d of supplementary calcium, and 9 patients were given placebo. At the end of the low and high salt regimens, we evaluated changes in blood pressure, platelet aggregation, and the platelet release reaction measured as plasma beta-thromboglobulin and platelet factor 4 levels. With high salt intake, significant increases in mean blood pressure (P < .02), red blood cell sodium (P < .01), and platelet aggregation induced by 3 mumol/L ADP (P < .01) and by 3.0 mg/L epinephrine (P < .05) were observed in the placebo-treated patients but not in the calcium-supplemented ones. Compared with the placebo-treated patients, calcium-supplemented patients had a smaller weight gain (P < .05) but excreted more sodium and calcium (P < .01) at the end of the high salt regimen. Calcium supplementation resulted in decreases in beta-thromboglobulin (P < .05), platelet factor 4 (P < .01), and plasma and urinary excretions of norepinephrine (P < .02) during the high salt, low calcium regimen. The decrease in plasma norepinephrine correlated positively with the decreases in beta-thromboglobulin (r = .72, P < .02) and platelet factor 4 (r = .85, P < .01).(ABSTRACT TRUNCATED AT 250 WORDS)

Inhibitory effect of insulin on vasopressin-induced intracellular calcium response is blunted in hyperinsulinemic hypertensive patients: role of membrane fatty acid composition.

Impaired insulin-mediated vasodilation has been implicated in hypertension that is associated with the metabolic syndrome. The aim of this study was to determine whether an abnormality in membrane fatty acid composition was related to a weakening of insulins inhibitory effect on agonist-stimulated intracellular free calcium elevation. Mild to moderate hypertensive patients (n = 27) and normotensive controls (n = 11) were studied. Hypertensive patients were divided into normoinsulinemic patients (n = 14) and hyperinsulinemic patients (n = 13) according to the area under the curve of plasma insulin concentrations during a 75-g oral glucose tolerance test. Nonstimulated and arginine-vasopressin (AVP) (1 µmol/l)-stimulated intraplatelet free calcium concentrations (p[Ca2+]i) were measured with or without insulin (100 µU/ml) preincubation. Platelet membrane fatty acid composition, intraerythrocyte sodium content, and the ouabain-sensitive sodium efflux rate constant (Kos) of erythrocytes were also determined. Insulin preincubation reduced AVP-stimulated p[Ca2+]i elevation in both normotensive controls and hypertensive patients. The inhibitory effect of insulin on AVP-stimulated elevation of p[Ca2+]i (%Inhibition) was significantly (P < 0.05) blunted in hyperinsulinemic hypertensive patients (9.7% ± 2.4%) as compared to normoinsulinemic hypertensive patients (17.4% ± 2.7%) and normotensive controls (16.9% ± 1.7%). In hypertensive patients, the %Inhibition was correlated negatively with saturated fatty acids (SFA) (r = −0.51, P < 0.05) and systolic blood pressure (r = −0.44, P < 0.05), and correlated positively with membrane polyunsaturated fatty acids (PUFA) (r = 0.53, P < 0.01) and Kos (r = 0.53, P < 0.005). Multiple regression analysis showed that SFA, PUFA, and Kos were the significant variables for %Inhibition. These findings indicate that an increase in SFA and a decrease in PUFA may cause insulin insensitivity in cellular calcium and sodium handling in hypertension with hyperinsulinemia.

Calcium Supplementation in Salt-Dependent Hypertension

To clarify the mechanism of the antihypertensive effect of oral Ca loading, we studied the effect of Ca supplementation on salt-induced blood pressure elevations in patients with essential hypertension and DOCA-salt hypertensive rats. When the diet was changed from low to high salt (300 mEq/day), the percent increase in mean blood pressure was smaller (p less than 0.01) in the Ca-supplemented (2,160 mg/day) patients than in the Ca-restricted (250 mg/day) ones. Oral Ca loading resulted in a smaller weight gain, a greater urinary sodium excretion, and an increase in red cell Mg. In the experimental study, high Ca (4% CaCl2) intake attenuated the blood pressure elevation in DOCA-salt-treated rats, accompanied with an increase in urinary sodium excretion, with the resultant attenuation in intra- and extracellular sodium retention. The decrease in catecholamine contents of hearts was improved, and a higher survival rate was observed in Ca-supplemented DOCA-salt rats. The results suggest that Ca supplementation may prevent a rise in BP in salt-dependent hypertension by inducing natriuresis with the resultant attenuation in sodium retention. The altered intracellular Mg level in hypertensive patients and the normalization of enhanced sympathetic nervous activity in DOCA-salt rats may, in part, be involved in its mechanism.