Tomoyuki Okuguchi

Significance of sympathetic nervous system in sodium-induced nocturnal hypertension

OBJECTIVE The purpose of this study was to investigate the effects of salt loading on circadian patterns of blood pressure (BP) and sympathetic nervous activity. SUBJECTS AND METHODS Seventy-six patients with essential hypertension were hospitalized and placed on a low-salt diet (2 g/day) for 7 days followed by a high-salt diet (20-23 g/day) for another 7 days. On the last day of each salt diet, 24 h ambulatory BP, plasma noradrenaline concentrations, urinary noradrenaline excretion, plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were measured. Patients whose average mean BP was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 44); the remaining patients, whose mean BP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 32). RESULTS Salt loading converted the circadian pattern of BP from dippers, whose mean BP during the night-time was decreased by more than 10% from the daytime BP, to non-dippers in the SS group but not in the NSS group. A nocturnal decrease in plasma noradrenaline concentration was unaffected after salt loading in the NSS group but dampened in the SS group. The night-time/daytime ratio of urinary noradrenaline excretion, which was increased after salt loading in the SS group only, was greater in the SS group than in the NSS group under the high-salt diet. The salt-induced suppression rate of PRA and PAC was similar between the SS and NSS groups. CONCLUSION BP fails to fall during the night under the high-salt diet in patients with the SS type of essential hypertension. This may be related to the lack of nocturnal decrease in sympathetic nervous activity.

Salt-induced exacerbation of morning surge in blood pressure in patients with essential hypertension

The morning surge in blood pressure (BP) is related to the morning occurrence of lethal cardiovascular events. We tested the hypothesis that salt intake may be associated with the morning surge in BP in essential hypertension. Seventy-six patients were admitted and placed on a low salt diet (2 g/day) for 7 days followed by a high salt diet (20–23 g/day) for another 7 days. At the end of each salt diet, 24-h ambulatory BP and heart rate monitorings and head-up tilt (HUT) test were performed. Patients whose average mean BP (MBP) was increased by more than 10% by salt loading were assigned to the salt-sensitive (SS) group (n = 37); the remaining patients, whose MBP was increased by less than 10%, were assigned to the non-salt-sensitive (NSS) group (n = 39). The increase in ambulatory MBP during 6.30–8.00 am above the baseline (2.00–4.00 am) was significantly enhanced by salt loading in the NSS group (P < 0.05), but not in the ss group. the coefficient of variation of 24-h mbp and heart rate was increased by salt loading only in the nss group. the significant elevation of plasma noradrenaline concentration after awakening, which was noted during the low salt diet period, was unchanged during the high salt diet period in the nss group, but abolished in the ss group. salt loading enhanced hut-induced decrease in systolic bp without affecting the heart rate response only in the nss group. we conclude that the morning surge in bp is enhanced by salt loading in the nss type of essential hyper- tension, presumably by the excessive activation of the sympathetic nervous system.

Nocturnal blood pressure decrease is associated with increased regional cerebral blood flow in patients with a history of ischemic stroke.

Background It remains controversial whether there is a J-shaped relationship between blood pressure and recurrent stroke among patients with a recent history of ischemic stroke. Objective To investigate the relationship between regional cerebral blood flow (rCBF) and the dipping of nocturnal blood pressure in patients receiving antihypertensive treatment after ischemic stroke. Methods and results Forty-seven patients with a previous history of ischemic stroke and 37 patients with a history of non-ischemic stroke underwent 24-h ambulatory blood pressure monitoring and rCBF measurement with single photon emission computed tomography. Of the 47 patients with ischemic stroke, 30 were diagnosed as having suffered atheromatous or embolic stroke, and 37 had an ischemic lesion in the territory of the carotid artery. Systolic and diastolic blood pressures during daytime and night-time were controlled at less than 140/90 mmHg by a low-salt diet or long-acting antihypertensive agents, or both. In patients with ischemic stroke, there were significant negative correlations between the percentage change in nocturnal blood pressure and rCBFs in the thalamus (r = −0.33, P = 0.02), putamen (r = −0.34, P = 0.02) and cerebral cortex (r = −0.31, P = 0.03). Multivariate analysis revealed that only the percentage change in nocturnal blood pressure was related to rCBF. There was a significant positive correlation between rCBFs in the thalamus and the cerebral cortex (r = 0.74, P < 0.05). In patients with non-ischemic stroke, there was no significant correlation between the percentage change in nocturnal blood pressure and rCBFs. Conclusions These findings indicate that the decrease in nocturnal blood pressure is associated with the increase in rCBF in patients with a history of ischemic stroke in the territory of the carotid artery.

Effect of losartan on nocturnal blood pressure in patients with stroke: comparison with angiotensin converting enzyme inhibitor

BACKGROUND Treatment of nocturnal hypertension has been reported to be beneficial for primary and secondary prevention of stroke. We compared the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme inhibitor (quinapril) on nocturnal blood pressure (BP) and sympathetic nervous activity in patients with hypertension and stroke. METHODS According to a prospective, randomized, cross-over design, 30 hypertensive patients with a previous history of stroke (25 hemorrhage, 5 infarction) were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regimen for an additional 4-week period. In the last week of each treatment, 24-h ambulatory BP monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. RESULTS Neither systolic nor diastolic BP during daytime differed between losartan and quinapril treatments, but those during nighttime were lower with losartan treatment than with quinapril treatment. The nocturnal decreases in systolic and diastolic BP were both greater with losartan treatment than with quinapril treatment (systolic BP: 6.1% +/- 5.9% v 2.5% +/- 6.9%, diastolic BP: 6.4% +/- 6.5% v 3.3% +/- 7.8%, both P <.05). The nocturnal decrease in urinary norepinephrine excretion was greater with losartan treatment than with quinapril treatment (52.8% +/- 9.7% v 42.8% +/- 17.2%, P <.05). CONCLUSIONS Losartan enhances the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke presumably by way of the suppression of nocturnal sympathetic nervous activity.

Sodium ionophore converts growth manner of vascular smooth muscle cells from spontaneously hypertensive rats.

OBJECTIVES Vasoconstrictor peptides such as endothelin (ET) cause hypertrophy of vascular smooth muscle cells (VSMC) in Wistar Kyoto rats (WKY) and hyperplasia in spontaneously hypertensive rats (SHR). They also induce an increase in Na+ concentration ([Na+]i) and activate protein kinase C (PKC) independently. Therefore, we tested the hypothesis that the increase in [Na+]i may be involved in the conversion of growth manner under activated PKC in SHR VSMC. METHODS AND RESULTS 10(-7) M phorbol ester (TPA) increased the diameter and protein content of VSMC from both strains under 18% serum conditions. Further addition of 10(-6) M gramicidin (Na+ ionophore) converted TPA-induced hypertrophy to hyperplasia, which was due to the quick transition from S to G2/M phase, only in SHR VSMC. Western blot analysis showed that serum- and TPA-induced tyrosine phosphorylation of mitogen-activated protein (MAP) kinase was potentiated by 10(-6) M gramicidin in SHR. [Na+]i, which was measured by sodium-binding benzofuran isophthalate (SBFI), was increased about 35 mM by 10(-6) M gramicidin in both strains, but TPA did not affect basal [Na+]i and the gramicidin-induced increase in [Na+]i. CONCLUSIONS We conclude that sodium ionophore may convert hypertrophy to hyperplasia synergistically with activated PKC in SHR VSMC, possibly by MAP kinase phosphorylation.

Comparison of the effects of losartan and angiotensin converting enzyme inhibitor on nocturnal blood pressure in patients with stroke

Abstract Background : Therapy of nocturnal hypertension was shown to be beneficial for primary and secondary prevention of stroke. We investigated the effects of angiotensin II antagonist (losartan) and angiotensin converting enzyme (ACE) inhibitor (quinapril) on nocturnal blood pressure and sympathetic nervous activity in patients with hypertension and stroke. Methods : According to a prospective, randomized, crossover design, 30 hypertensive patients with a previous history of stroke were assigned randomly to receive losartan (50 mg) or quinapril (10 mg) once daily for 4 weeks. The patients were switched to the alternative regime for an additional 4-week period. In the last week of each treatment, 24-h ambulatory blood pressure (BP) monitoring was performed every 30 min, and 24-h urine was collected for the measurement of catecholamine. Results : Neither systolic nor diastolic BPs during daytime differed between losartan and quinapril treatments, but those during nighttime were lower under losartan treatment than under quinapril treatment. The nocturnal decreases in systolic and diastolic BPs were both greater under losartan treatment than under quinapril treatment. The nocturnal decrease in urinary norepinephrine (NE) excretion was greater under losartan treatment than under quinapril treatment. Conclusions : Losartan augments the nocturnal decrease in ambulatory BP compared with that of quinapril in patients with a previous history of stroke, presumably via the suppression of nocturnal sympathetic nervous activity.