We sought to determine whether a family history of hypertension is quantitatively associated with the prevalence of hypertension and blood pressure in a screened cohort. Clinical data and family (parents and siblings) histories regarding hypertension were collected from 9,914 individuals (probands) who were interviewed and examined during a one-day clinic by the Okinawa General Health Maintenance Association in 1997. We used logistic analysis to calculate odds ratios with adjustments for age, sex, body mass index, total cholesterol, presence of diabetes mellitus, alcohol use, cigarette smoking, and status of physical exercise. The age- and sex-adjusted hypertension prevalences in probands were 29.0% for those with 1 family member with a history of hypertension (n=2,112), 37.6% for those with 2 hypertensive family members (n=374), and 47.3% for those with 3 or more hypertensive family members (n=68). In contrast, only 16.4% of probands who reported no family history of hypertension (n=7,360) were hypertensive themselves. The trend of the prevalence according to the number of family members with a history of hypertension was significantly positive (p=0.003). The adjusted odds ratios (95% confidence interval) of hypertension were 2.74 (2.43-3.10) for 1 member, 4.62 (3.62-5.90) for 2 members, and 6.04 (3.51-10.4) for 3 or more members with a history of hypertension. In patients without antihypertensive medication (n=9,009), systolic/diastolic blood pressure (mean +/- SD) was 121 +/- 17/75 +/- 11 for 1 member, 124 +/- 18/77 +/- 12 for 2 members, and 127 +/- 17/78 +/- 11 for 3 or more members with a history of hypertension. In contrast, the mean systolic/diastolic blood pressure of probands who reported no family history of hypertension (n=7,360) was 119 +/- 15/74 +/- 10 mmHg, which was significantly (p<0.05) lower than that of any of the groups with hypertensive family members. In conclusion, an increase in the number of family members with hypertension was associated with an increasing prevalence of hypertension and blood pressure in the probands, independent of conventional risk factors for hypertension. Family members of hypertensive subjects may need to be treated in primary prevention efforts related to hypertension.

This randomized, placebo-controlled within dose groups, double-blind, single rising dose study investigated the safety, tolerability, pharmacokinetics and pharmacodynamics of 1 mg to 100 mg doses of empagliflozin in 48 healthy Japanese male subjects. Empagliflozin was rapidly absorbed, reaching peak levels in 1.25 to 2.50 h; thereafter, plasma concentrations declined in a biphasic fashion, with mean terminal elimination half-life ranging from 7.76 to 11.7 h. Increase in empagliflozin exposure was proportional to dose. Oral clearance was dose independent and ranged from 140 to 172 mL/min. In the 24 h following 100 mg empagliflozin administration, the mean (%CV) amount of glucose excreted in urine was 74.3 (17.1) g. The amount and the maximum rate of glucose excreted via urine increased with dose of empagliflozin. Nine adverse events, all of mild intensity, were reported by 8 subjects (7 with empagliflozin and 1 with the placebo). No hypoglycemia was reported. In conclusion, 1 mg to 100 mg doses of empagliflozin had a good safety and tolerability profile in healthy Japanese male subjects. Exposure to empagliflozin was dose proportional. The amount and rate of urinary glucose excretion were higher with empagliflozin than with the placebo, and increased with empagliflozin dose.

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Clustering of risk factors was significantly associated with hypertension. The number of risk factors positively correlated with the blood pressure levels in nonhypertensive subjects. The accumulation of risk factors may play an important role in the pathogenesis of hypertension, and thus the aggregation of risk factors may need to be addressed in primary prevention efforts related to hypertension.

The aim of the present study was to examine the effects of L-glutamate and glycine microinjected into the rostral ventrolateral medulla (RVLM) in conscious unrestrained rats. Microinjection of 2 nmol of L-glutamate increased the mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA) in the conscious rats. The RSNA responses were significantly larger in the conscious rats than in anesthetized rats, while the magnitude of the pressor responses was similar in conscious and urethane-anesthetized rats. L-Glutamate injection significantly decreased heart rate in the conscious rats, whereas it increased the heart rate slightly but not significantly in the anesthetized rats. Microinjection of 100 nmol of glycine into the RVLM of conscious rat decreased MAP and RSNA. In 2 of the 6 rats examined, the depressor and sympathoinhibitory responses were preceded by a few seconds of a pressor and sympathoexcitatory phase. The decreases of RSNA in response to glycine injection were significantly larger in the conscious rats than in the anesthetized rats, whereas the magnitude of the depressor responses was similar in the two groups of rats. Heart rate decreased in response to glycine injection into the RVLM in the conscious and the anesthetized rats. In conclusion, in conscious unrestrained rats, as well as in urethane-anesthetized rats, L-glutamate acts as a sympathoexcitatory agent and glycine acts as a sympathoinhibitory agent in the RVLM. The sympathetic responses to these amino acids are larger in conscious rats than in anesthetized rats.