Fumiaki Nakamura

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Role of cardiac angiotensin II in isoproterenol-induced left ventricular hypertrophy.

Angiotensin II (Ang II) has been shown to induce proliferation of cardiac myocytes. To examine the role of Ang II in left ventricular (LV) hypertrophy, isoproterenol was infused subcutaneously into 9-week-old male Wistar rats at 4.2 mg/kg/day for 7 days. Infusion of isoproterenol increased LV weight and Ang II concentrations in plasma and in LV tissue. In anephric rats, LV weight and tissue Ang II were increased similarly, but plasma Ang II was not changed by isoproterenol. Concomitant oral administration of trandolapril and isoproterenol prevented increases in both LV Ang II and LV weight. Treatment with hydralazine decreased blood pressure in a similar way as trandolapril but did not affect either LV weight or LV Ang II. Plasma Ang II was not decreased by either trandolapril or hydralazine when administered in combination with isoproterenol. These results suggest that cardiac tissue Ang II regulates myocyte growth in isoproterenol-induced LV hypertrophy, and the reduction of Ang II partly explains the prevention of cardiac hypertrophy by the converting enzyme inhibitor.

Role of angiotensin II in high fructose-induced left ventricular hypertrophy in rats.

Recent studies suggest the linkage of hypertension and insulin resistance. High fructose diet is known to induce hyperinsulinemia and hypertension in rats. In a previous study, however, high fructose (66%) diet failed to elevate blood pressure but increased left ventricular weight in Sprague-Dawley rats. In the present study, we investigated the precise mechanism of high fructose diet-induced changes in the cardiovascular system in rats. Intake of fructose-enriched diet for 2 weeks increased serum insulin and plasma angiotensin II levels. Urinary excretion of sodium and norepinephrine was not changed. Blood pressure measured directly through an indwelling catheter was not increased, but left ventricular weight and protein content were increased by high fructose diet. To further elucidate the role of the renin-angiotensin system, an angiotensin II type 1 receptor antagonist, TCV-116, was given orally at 1 mg/kg per day with either normal or high fructose diet. Concomitant administration of TCV-116 did not affect plasma glucose or serum insulin levels. Plasma angiotensin II was increased, but neither urinary sodium nor norepinephrine was changed by TCV-116. TCV-116 similarly decreased blood pressure in rats on normal and high fructose diets. Increase in left ventricular weight induced by high fructose diet was prevented by the concomitant administration of TCV-116. On the other hand, left ventricular weight in control rats was not changed by TCV-116. In conclusion, increased plasma angiotensin II may account for the left ventricular hypertrophy induced by high fructose diet, whereas hemodynamic change, sodium retention, and the sympathetic nervous system do not play an important role.

EFFECT OF AN ANTIHYPERTENSIVE DRUG ON BRAIN ANGIOTENSIN II LEVELS IN RENAL AND SPONTANEOUSLY HYPERTENSIVE RATS

1. Although numerous studies suggest that brain angiotensin (AII) may play an important role in the regulation of blood pressure, it is still unclear what factors may influence brain All. In this study, we hypothesized that brain AII is influenced by circulating factors. To investigate the role of blood pressure and plasma All in brain AII level, we studied the effect of an antihypertensive drug on brain AII in two‐kidney, one‐clip (2K1C) and spontaneously hypertensive (SHR) rats.

THE ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR, PERINDOPRIL, PREVENTS CARDIAC HYPERTROPHY IN LOW‐RENIN HYPERTENSIVE RATS

1. To examine whether an angiotensin‐converting enzyme (ACE) inhibitor prevents left ventricular (LV) hypertrophy even in low‐renin hypertension, we studied the effect of the administration of perindopril on cardiac hypertrophy induced by partial renal ablation in hypertensive rats.

Impact of azelnidipine treatment on left ventricular diastolic performance in patients with hypertension and mild diastolic dysfunction: multi-center study with echocardiography.

We investigated the impact of lowering blood pressure (BP) with azelnidipine, a newly developed calcium channel blocker, generation on the left ventricular (LV) diastolic function and LV filling pressure by assessing non-invasive indices derived from echo Doppler study. This study evaluated 232 hypertensive patients with diastolic dysfunction. This study had two groups: (1) in which azelnidipine was administered to patients as a first-line therapy, and (2) in which amlodipine was converted to azelnidipine. Early diastolic mitral annulus velocity (e′, cm s−1), the ratio of peak E velocity to e′ velocity (E/e′ ratio) and level of brain natriuretic peptide (BNP) were measured before and, an average of, 8 months after azelnidipine treatment. In the first-line azelnidipine group, the systolic and diastolic BP reduced by 26 and 11 mm Hg, respectively. The e′ increased, and E/e′ ratio and BNP level decreased significantly. In the converted-from-amlodipine group, the systolic and diastolic BP decreased by 14 and 6 mmHg, respectively. The e′ velocity increased, but the E/e′ ratio and BNP level did not change. In both groups, azelnidipine lowered BP and improved LV diastolic function (an increase in the e′ velocity). Possible reduction in LV filling pressure (a decrease in the E/e′ ratio and BNP level) is observed only in the first-line azelnidipine group.

Predominance of Nocturnal Sympathetic Nervous Activity in Salt-Sensitive Normotensive Subjects

To assess the relation between salt sensitivity and autonomic nervous function by power spectral analysis of heart rate variability in normotensive subjects, low and high salt diets were given to 13 normotensive men (aged 25 to 39 years) for 4 days each. Autonomic function was assessed by power spectral analysis of R-R intervals based on an autoregressive algorithm from 24-h Holter electrocardiogram. Subjects whose mean blood pressure was increased more than 3 mm Hg by high salt diet were defined as salt sensitive (SS, n = 5), and the remainder as salt resistant (SR, n = 8). Using the low frequency (LF, 0.1 Hz) and high frequency (HF, 0.25 Hz) components, the LF to total power ratio (%LF) was used as a marker of sympathetic activity, and the HF to total power ratio (%HF) as a marker of parasympathetic activity. Compared to the daytime, SR revealed a decrease in %LF and an increase in %HF during the night on both diets. In SS, these circadian changes were observed only during low-salt diet. During the night, SS showed a higher %LF and a lower %HF than SR. Plasma catecholamines tended to be decreased by the high sodium diet in SR but not in SS subjects. These results suggest that the persistent nocturnal predominance of sympathetic nervous activity in a salt-sensitive men may contribute to the subsequent increase of blood pressure in these subjects.

EFFECT OF LONG‐TERM TREATMENT WITH AN ANGIOTENSIN‐CONVERTING ENZYME INHIBITOR ON THE RENIN‐ANGIOTENSIN SYSTEM IN SPONTANEOUSLY HYPERTENSIVE RATS

1. To obtain information on regulation of the brain renin–angiotensin system, the effect of long‐term administration of angiotensin‐converting enzyme (ACE) inhibitor on brain renin and angiotensinogen mRNA was studied.

Cross-Sectional Survey of Workload and Burnout Among Japanese Physicians Working in Stroke Care The Nationwide Survey of Acute Stroke Care Capacity for Proper Designation of Comprehensive Stroke Center in Japan (J-ASPECT) Study

Background—Burnout is common among physicians and affects the quality of care. We aimed to determine the prevalence of burnout among Japanese physicians working in stroke care and evaluate personal and professional characteristics associated with burnout. Methods and Results—A cross-sectional design was used to develop and distribute a survey to 11 211 physicians. Physician burnout was assessed using the Maslach Burnout Inventory General Survey. The predictors of burnout and the relationships among them were identified by multivariable logistic regression analysis. A total of 2724 (25.3%) physicians returned the surveys. After excluding those who were not working in stroke care or did not complete the survey appropriately, 2564 surveys were analyzed. Analysis of the participants’ scores revealed that 41.1% were burned out. Multivariable analysis indicated that number of hours worked per week is positively associated with burnout. Hours slept per night, day-offs per week, years of experience, as well as income, are inversely associated with burnout. Short Form 36 mental health subscale was also inversely associated with burnout. Conclusions—The primary risk factors for burnout are heavy workload, short sleep duration, relatively little experience, and low mental quality of life. Prospective research is required to confirm these findings and develop programs for preventing burnout.

DISCREPANCY BETWEEN RENIN mRNA AND PLASMA RENIN LEVEL IN ANGIOTENSIN-CONVERTING ENZYME INHIBITOR-TREATED RATS

1. To investigate the role of transcriptional and post‐transcriptional factors in increasing renin synthesis secondary to angiotensin‐converting enzyme (ACE) inhibitors, we studied the changes in levels of renal renin mRNA, plasma renin and other hormonal factors.