Manabu Koga

INFLUENCE OF WORKLOAD ON THE ANTIHYPERTENSIVE EFFECT OF EXERCISE

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CROSSOVER COMPARISON BETWEEN THE DEPRESSOR EFFECTS OF LOW AND HIGH WORK-RATE EXERCISE IN MILD HYPERTENSION

1. The relationship between work‐rate and the antihypertensive effect of exercise in hypertensives, and the mechanism of that effect, were investigated by a crossover clinical trial.

Mild exercise activates renal dopamine system in mild hypertensives

Objective: The role of renal dopamine in the early depressor effect of exercise was evaluated in hypertensives. Methods: After a general clinical observation period of 4 weeks, 29 essential hypertensives were divided into two groups. The exercise group (n = 16) underwent blood lactate threshold exercise using a cycle ergometer for 60 min three times a week for 4 weeks. Results: In the non-exercise group (n = 13), blood pressure (BP) and humoral variables did not change significantly (from 150 ± 3/93 ± 2 to 145 ± 2/94 ± 1 mm Hg). In the exercise group (n = 16), resting BP was significantly reduced from 158 ± 2/92 ± 2 at week 0 to 145 ± 3/85 ± 3 mm Hg at week 4. The increase in urinary free dopamine excretion (from 248 ± 14 to 276 ± 24 ng/mg Cr) at week 4 was significantly higher than that in the non-exercise group (from 220 ± 31 to 196 ± 27 ng/mg Cr). In the exercise group, urinary kallikrein activity also increased significantly from 173.0 ± 35.4 at week 0 to 320.3 ± 63.3 ng bradykinin/min/mg Cr at week 4. These changes in urinary free dopamine excretion and urinary kallikrein activity were negatively correlated with the change in BP. The change in urinary sodium excretion was also negatively correlated with the change in plasma volume index. Moreover, the change in urinary free dopamine excretion was positively correlated with the changes in urinary kallikrein activity and urinary sodium excretion. The change in renal decarboxylation rate of DOPA (3,4-dihydroxyphenylalanine) positively correlated with the changes in urinary free dopamine excretion and urinary sodium excretion, and was negatively correlated with the change in systolic BP. Conclusion: These results suggest that exercise triggered renal dopamine generation and activation of renal kallikrein-kinin system, resulting in natriuresis and BP reduction in the early phase (4 weeks) of mild exercise.

Urinary kallikrein activity is increased during the first few weeks of exercise training in essential hypertension

Objective To determine whether the renal kallikrein–kinin and dopamine systems participate in lowering blood pressure during mild exercise in hypertensives. Design After a general clinical observation period of 4 weeks, 27 essential hypertensives were divided into two groups. The exercise group underwent blood lactate threshold exercise, using a cycle ergometer for 60 min three times a week for 10 weeks. The non-exercise group was observed at the outpatient clinic. Blood pressure and humoral parameters were measured at weeks 0, 1, 2, 4 and 10 in both groups. Methods Blood pressure was measured indirectly with an automatic blood pressure recorder. Twenty-four-hour urinary kallikrein activity (by kininogenase assay), total or free dopamine and total noradrenaline (by high-performance liquid chromatography) were also measured. Results In the non-exercise group blood pressure and humoral parameters did not change. In the exercise group the change in resting blood pressure between weeks 0 and 10 was statistically significant. The change in 24-h urinary kallikrein activity of the exercise group was significantly greater than that of the non-exercise group between weeks 0 and 1 and weeks 0 and 2. Moreover, the change in systolic blood pressure (SBP) between weeks 0 and 2 was negatively correlated with the change in urinary kallikrein activity between weeks 0 and 2, the change in total dopamine between weeks 0 and 2 was negatively correlated with the change in diastolic blood pressure in the same period, and the change in SBP between weeks 0 and 10 was positively correlated with the change in total noradrenaline in the same period in the exercise group. Subjects with a relatively high baseline urinary kallikrein activity had a significantly greater change in SBP between weeks 0 and 10 than subjects with a relatively low baseline activity. Conclusions The renal kallikrein—kinin and dopamine systems may participate in lowering blood pressure during the first few weeks of exercise training. The subsequent reduction of sympathetic activity may be involved in maintaining the lowered blood pressure. Mild exercise is more effective in reducing blood pressure in hypertensives who have a relatively high basal renal kallikrein-kinin system activity.

Changes of dopamine and atrial natriuretic factor by mild exercise for hypertensives

Changes of humoral factors related to the regulation of fluid volume were investigated in exercise training for hypertensives. Twelve patients with essential hypertension were treated with an aerobic exercise for 10 weeks. A significant reduction in blood pressure from 161 +/- 3/100 +/- 2 mmHg at week 0 to 142 +/- 5/94 +/- 3 mmHg at week 4 was observed which continued until week 10. Urine dopamine was increased significantly at the 4th week from 386 +/- 29.4 micrograms/day at week 0 to 524 +/- 46.3 micrograms/day and plasma atrial natriuretic factor (ANF) was significantly reduced at the 4th week, from 41.5 +/- 2.7 pg/ml at week 0 to 32.6 +/- 3.7 pg/ml. Plasma volume was found reduced significantly from 2,531 +/- 166 ml/m2 at week 0 to 2,221 +/- 165 ml/m2 at week 10. These results suggest that the increase of dopamine and reduction of plasma ANF which took place at the early stage might be related to, at least in part, the depletion of plasma volume and the reduction of blood pressure in mild exercise for hypertensives.

Structure of a kallikrein-like enzyme and its tissue localization in the dog

We previously purified a kallikrein-like enzyme from the dog heart and demonstrated that it is not only able to form kinins but can also convert angiotensin (Ang) I to Ang II. The aim of the present study was to clarify the structure and tissue localization of this enzyme. Western blot analysis of various canine tissues was performed with antiserum against the purified dog heart enzyme. The purified enzyme was subjected to a determination of its amino acid composition and a sequence analysis. Western blotting indicated that this enzyme was present in the heart, aorta, kidney, pancreas, lung, liver, spleen, small intestine, and skeletal muscle. The amino acid composition of the enzyme was different from that of dog urinary kallikrein. Amino acid sequence analysis indicated that it is likely to be N-terminally blocked. The present study showed that this kallikrein-like enzyme is different from previously reported kallikrein and is distributed not only in the heart, but also in other tissues such as the aorta, kidney, lung, liver, spleen, small intestine, and skeletal muscle. This enzyme may exert local effects by generating kinins and Ang II.

Plasma renin activity could be a useful predictor of left ventricular hypertrophy in essential hypertensives.

To clarify the ability of clinical and laboratory parameters to reflect target organ damage, especially left ventricular hypertrophy (LVH), we investigated which of these parameters might correlate to LVH as determined by electrocardiographic voltage at the first clinic visit in 108 (53 males and 55 females, average age 52 ± 10 years) untreated essential hypertensives. The sum of the amplitude of the S wave in lead V1 plus that of the R wave in lead V5 or V6 (SV1 + R(V5, V6)) was correlated with blood pressure in both males and females. In subjects with LVH (SV1 + R(V5, V6) ⩾ 3.5mV), a stepwise multiple regression analysis revealed that SV1 + R(V5, V6) was associated with plasma renin activity (PRA) in both males and females, and with creatinine concentration (Cr) in males. These results suggest that PRA at the first visit could be a useful predictor of LVH in patients with essential hypertension.

Active and inactive renin after exercise

SummaryThe effects of graded exercise on plasma concentrations of active and inactive renin were studied in seven healthy men. Exercise was performed on a cycle ergometer at four different exercise intensities (corresponding to 30%, 50%, 80% and 87% of

Roles of Renal Dopamine and Kallikrein-Kinin Systems in Antihypertensive Mechanisms of Exercise in Rats

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