To clarify the mechanism for cold-related thrombosis, we evaluated responses of blood pressure, platelet function, and sympathetic nervous activity after cold exposure in ten healthy male volunteers (33 +/- 2 years old). Mean blood pressure, beta-thromboglobulin, platelet factor 4, and plasma noradrenaline were increased after cold exposure associated with significant falls in skin, oral, and urine temperature. The increase in plasma noradrenaline significantly correlated with the change in platelet aggregation (3 microM ADP: r = 0.73, P less than .02, 3.0 micrograms/mL epinephrine: r = 0.65, P less than .05), and with mean blood pressure in the warn environment (r = 0.76, P less than .02). These results suggest that the cold-related increase in sympathetic nervous activity may contribute to enhancement of platelet function. This provides a possible explanation for the risk of thrombosis in cold weather in essential hypertension.

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.

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.

This study was designed to clarify the effects of orally administered eicosapentaenoic acid (EPA) on blood pressure, intracellular sodium content, and cell membrane fatty acid composition in patients with essential hypertension. After a 4-week run-in period, a study group of 17 male patients was assigned to an 8-week treatment with EPA (2.7 g/day) or placebo in a randomized, double-blind fashion with a crossover at week 4. Systolic blood pressure (SBP) was lower after treatment with EPA than after treatment with placebo (152.9+/-17.3 vs. 162.6+/-20.6 mmHg; p<0.01), while diastolic blood pressure was not statistically different. Compared with the placebo treatment, EPA supplementation resulted in a decrease in intraerythrocyte sodium content (R-Na; 11.17+/-0.63 vs. 10.44+/-1.28 nmol/l cells; p<0.05) accompanied by an increase (p<0.001) in erythrocyte membrane EPA content. The increase in membrane EPA content was related to the decrease in SBP (r=-0.52, p<0.05) and the decrease in R-Na (r=-0.57, p<0.02) during EPA treatment. The decrease in R-Na correlated positively with the decrease in SBP (r=0.54, p<0.05), and correlated negatively with the change in Na+-K+ ATPase activity (r= -0.59, p<0.02). However, the change in Na+-K+ ATPase activity did not directly correlate with the change in membrane EPA content. In conclusion, oral EPA supplementation increased membrane EPA content and reduced SBP in patients with essential hypertension. Based on the association between the increase in membrane EPA content and the decrease in intracellular sodium concentration, EPA may lower blood pressure by altering the activities of the membrane sodium transport systems.

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<0.0l). The Ca group showed a smaller weight gain (p<0.05) and a greater urinary excretion of sodium (/»<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<0.01), which was correlated inversely with the salt-induced changes hi mean blood pressure (r=-0.54, p<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. The intracellular magnesium level may, in part, be involved in the regulation of salt-induced blood pressure response, although the pathophysiological mechanism remained unexplored. (Hypertension 1989; 13:219-226) A bnormalities of calcium homeostasis have Z A recently been considered to be important in JL JL. the pathogenesis of essential hypertension. Clinical studies indicate enhanced urinary calcium leak 1 and lower levels of serum ionized calcium, especially in those with low plasma renin activity. 23Epidemiological studies have also suggested an inverse relation between the level of calcium intake and the incidence of hypertension.4 All of these reports suggest an important role for calcium deficiency in genetic hypertension, and intervention studies have indicated that oral calcium supplementation is associated with a lowering of blood pressure in young normotensive adults, 3 normal pregnant women, 6 and patients with mild to moderate hypertension, 7 -9 although the mechanism of the hypotensive effect of oral calcium remains unclear.