Kikuo Arakawa

Role of left ventricular regional nonuniformity in hypertensive diastolic dysfunction

OBJECTIVES This study investigated 1) the role of left ventricular diastolic nonuniformity in hypertensive left ventricular diastolic dysfunction, and 2) the effects of a calcium channel antagonist on diastolic nonuniformity in hypertensive and normotensive subjects. BACKGROUND Augmented left ventricular diastolic nonuniformity contributes to diastolic dysfunction in hypertrophic cardiomyopathy. Impaired left ventricular diastolic function with preserved systolic function has been recognized in hypertension. Therefore, abnormal ventricular regional nonuniformity might also be involved in hypertensive diastolic dysfunction in a milder form of hypertrophy. METHODS Thirteen patients with established hypertension underwent radionuclide ventriculography before and after nifedipine administration. Indexes of left ventricular function were derived by computer analysis of the time-activity curve. After a computer subdivided the left ventricle into four regions, a time-activity curve of each region was constructed to determine an index of left ventricular diastolic nonuniformity. This index was calculated as the sum of the absolute values of time difference between global and regional peak filling in the septal, the apical and the lateral region. Ten normotensive subjects were studied for comparison. Echocardiography was performed in both groups. RESULTS The two groups were matched for age, gender, heart rate, echocardiographic dimensions and systolic function. In the hypertensive group, left ventricular diastolic filling indexes were impaired, with a negative correlation between peak filling rate and the diastolic nonuniformity index. Although the change in ejection fraction after nifedipine administration was similar in the two groups, the increase in peak filling rate was larger in the hypertensive patients. The diastolic nonuniformity index decreased after nifedipine in the hypertensive but not in the control group. This decrease correlated with improved peak filling rate in the hypertensive group. CONCLUSIONS In hypertensive patients with preserved systolic function, left ventricular diastolic nonuniformity increases, causing early diastolic dysfunction. Decreased diastolic nonuniformity after pharmacologic intervention contributes to lessened ventricular filling dysfunction, regardless of changes in loading conditions in hypertension. Thus, diastolic nonuniformity is an important determinant of left ventricular filling abnormality and might be a target of pharmacologic intervention in hypertensive patients.

Substrate-dependent angiotensin II formation in the peripheral circulation

An alternative angiotensin II-forming system distinct from the vascular renin-angiotensin system was demonstrated using a rat hindlimb perfusion system and synthetic substrates. This pathway was resistant to captopril and aprotinin, but was highly sensitive to chymostatin. Moreover, angiotensin II formation was substrate-dependent, i.e. angiotensin II formation from tridecapeptide human renin substrate in the presence of captopril was more than twice than that from an equimolar amount of angiotensin I. Both pathways may play a role in regulating the peripheral circulation.

Angiotensin-Converting Activity of Tissue Kallikrein

This study examined the ability of tissue kallikreins, purified from both rat submandibular gland (SMG) and human urine, to form angiotensin II from synthetic angiotensin I. Both kallikreins converted angiotensin I to angiotensin II at neutral pH with the following kinetic constants: SMG kallikrein, Km = 9.43 x 10(-5) mol/l, Kcat = 1.58 mumols/mg protein/min; human urinary kallikrein, Km = 1.71 x 10(-4) mol/l, Kcat = 0.06 mumol/mg protein/min. These activities were not affected by angiotensin-converting enzyme (ACE) inhibitor. These results suggest that tissue kallikrein might participate in the formation of angiotensin II during administration of an ACE inhibitor.

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

CARDIAC EFFECTS OF LOCAL ANGIOTENSIN-CONVERTING ENZYME INHIBITION IN HYPERTENSIVE PATIENTS

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Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs

) for 10 min each. Concentrations of active renin and total renin after activation by trypsin were measured by direct immunoradiometric assay. Non-trypsin-activated renin concentration (inactive) was obtained by subtraction. Active renin concentrations at 30%, 50%, 80% and 87% of

Direct Formation of Angiotensin II without Renin or Converting Enzyme in the Ischemic Dog Heart

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