The characteristics of left ventricular ejection (velocity and extent of wall shortening) can be analyzed in relation to the appropriateness of the matching between afterload and the level of inotropic state ( contractility), as modified by the preload (Frank-Starling) reserve. In the normal left ventricle if the preload is not allowed to compensate for and acute increase in afterload, or if the limit of preload reserve is reached, velocity (V_CF) and stroke volume will diminish; that is, an afterload mismatch occurs. This acute mismatch can be corrected by administration of a positive inotropic agent. In normal conscious animals and in man the ejection phase measures in the basal state (such as ejection fraction, and V_CF corrected for heart size) encompass a relatively narrow range, and when the normal heart adapts successfully to a chronic pressure or volume overload such measures remain normal per unit of muscle. These findings provide the basis for their use in detecting a depressed basal level of inotropic state, even in the presence of certain valvular lesions. When there is mild depression of the basal inotropic state, enhanced preload and dilatation can allow full compensation of V_CF, but acute pressure loading can allow detection of the reduced preload reserve by inducing a substantial fall in stroke volume and V_CF. When the basal inotropic state is greatly reduced, a mismatch between afterload and contractility, expressed as reduced V_CF or ejection function, will become evident in the basal state even if the afterload is normal. Any increase in aortic pressure will then cause a sharp reduction in stroke volume or V_CF. Also, under these circumstances therapeutic afterload reduction with agents such as nitroprusside can increase velocity and extent of wall shortening, and the cardiac output, providing the preload is maintained. The concept of afterload mismatch with limited preload reserve provides a framework for understanding the behavior of the normal or depressed ventricle and how it can operate on a "descending limb" of function. It helps to explain why measures of the ejecting phase (which are sensitive to afterload) appear to be more reliable than isovolumic phase indices (which are relatively insensitive to afterload) for detecting depressed basal inotropic state. Finally, the concept allows for interpretation of the responses observed in the clinical setting to acute and chronic increases and decreases in loading conditions on the left ventricle.

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Labelled proline incorporation into collagenous and noncollagenous proteins of aorta or mesenteric arteries was significantly increased in 70-day-old spontaneously hypertensive rats (SHR) at the early stage of hypertension in comparison with normotensive Wistar-Kyoto (WK) rats; however such an increase was not detected in 30-day-old SHR at the prehypertensive stage. Similar increases in the proline incorporation were noted in 70-day-old renal hypertensive rats and in DOCA hypertensive rats in which hypertension had been induced similarly to that in SHR. Furthermore, the decay of the specific activity of noncollagenous and collagenous proteins was studied for 100 days after labelled proline infusion. The decay of the noncollagenous protein activity was clearly accelerated in the heart, aorta and especially in the mesenteric arteries of SHR compared with WK. The decrease in the hydroxyproline radioactivity of the collagenous protein was significantly faster in the aorta and mesenteric arteries in SHR. These results proved the increased protein metabolism in the arterial walls in the relatively early stage of hypertension in SHR as well as in experimental hypertension, and then suggested its improtance in the common pathogenetic mechanisms of hypertension.

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The stroke-prone and stroke-resistant substrains of the spontaneously hypertensive rat (SHR) were employed for an evaluation of possible role of renin-angiotensin system and of water and electrolyte balances in inducing hypertensive vascular lesion. Serial study on plasma renin level and vascular changes did not support the hypothesis that plasma renin is a major risk factor in the development of cardiovascular complications. The high plasma renin level seen in advanced stages of hypertension appeared to be a result of severe vascular damages, indicating malignant transformation of hypertension. In this state, water turnover was enhanced without any abnormality in electrolyte balance. A possible mechanism involved in the malignant course of hypertension is discussed.

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Renin inhibitory effects of about 30 kinds of newly synthesized Phosphatidyl-E and Phosphoryl-E were studied in vitro and in vivo. Among the synthetic Phosphatidyl-E, PE (β-C⁼³₁₈, γ-C₁₈) series were the most potent and these were stronger than natural Phosphatidyl-E. We also confirmed that the conversion from the original Phosphatidyl-E, so called prerenininhibitor, to lyso-form to exhibit renin inhibition as mentioned by Sen et al. and Baggio et al. was not essential. But a stronger inhibition to renin was observed in PE-72, one of synthetic Phosphoryl-E analogues. PE-104, Phosphoryl-E without long fatty acid chain, was the most potent inhibitor in this study. PE-72 and PE-104 inhibited the reaction between dog renin and substrate in a competitive way. In dogs and rats, Phosphoryl-E decreased hypertensive responce and increased angiotensin I concentration induced by the exogenous renin. Hypotensive effects of Phosphatidyl-E and Phosphoryl-E were also demonstrated in renal hypertensive rats and not in normotensive rats.

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Plasma renin activity and aldosterone were measured simultaneously in 67 out-patients with essential hypertension. High aldosterone was more often in patients with high renin, and low levels of aldosterone were usual in those with low or normal renin. In order to study the mechanism by which aldosterone and renin activity are suppressed in low-renin hypertension, 25 patients (13 normal-renin hypertensives, 10 low renin patients including 4 non-responders and two DOC excess hypertensives) were investigated as inpatients. Plasma renin activity, aldosterone and cortisol were determined by the following stimulations with 3 days of sodium restriction and 2 hours of upright posture, angiotensin II infusion (at a dose which increased 20mmHg of diastolic blood pressure), ACTH administration (rapid i.m. injection of 0.25 mg of alpha 1-24 preparation) and potassium infusion (30meq of potassium i.v.). Responses of aldosterone in normal-renin hypertensives to all stimulations were 3-5 fold increases from base line values. Low renin hypertensives except two of four non-responders showed the responses similar to those in normal-renin patients. The responses of two of the non-responders were similar to those in DOC excess hypertensives who showed reduced responses of aldosterone to some of these stimulations. Thus, it seems that low-renin hypertension is a clinical entity caused by a variety of mechanisms, and the mechanism by which low-renin hypertension is induced is not explained by one factor such as an unknown mineralocorticoid.

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Plasma catecholamine (CA) levels in the coronary sinus (CS), aorta (Ao) and femoral vein (FV) were simultaneously measured in 22 patients with various heart diseases at rest and during handgrip exercise (IHG). The mean resting levels of plasma norepinephrine (NE) in CS, Ao and FV were 359±49 (SEM) pg/ml, 290±27 and 234±24, respectively. The corresponding values of epinephrine (E) were 127±18 pg/ml, 186±30 and 97±11, respectively. The E values in Ao were significantly greater than those in CS and in FV (p<0.05). IHG exercise induced an obvious elevation of plasma CA levels in every portion of the circulation studied. The mean increments of NE concentration were 81%, 54% and 67% of the resting levels at CS, Ao and FV respectively, while IHG induced elevation of E were 70% of the resting values at each portion studied. Significant correlations were observed between individual CA concentrations in CS and in Ao, and also between those in Ao and in FV at rest. Under raised sympathoadrenal conditions, however, individual values of NE in CS failed to correlate significantly to those in Ao and in FV, respectively. The NE output from CS was limited to only 3% and 5% of those in Ao at rest and during IHG, respectively. An actual mean increment of NE on its passing through the coronary circulation was only 2% or less of NE output in Ao at both stages. It appears, thus, to be untenable that the cardiac tissue is one of the major source of circulating CA at physiological condition. From these reasons, the direct measurement of NE levels in CS may be mandatory, when plasma CA assay is designed for the purpose of studying the role of the sympathetic nerve activity in the regulation of cardiac function.

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The present investigation examined the relationship between renin release and renal autoregulation of blood flow in the anesthetized dogs. A reduction in renal arterial pressure from control pressure to 100mmHg changed neither the flow rates of all cortex zones nor renin secretion. Further reductions of renal arterial pressure to 70mmHg and 50mmHg resulted in a significant increase of renin secretion and a decrease of blood flow in the outer cortex. Intrarenal arterial infusion of acetylcholine abolished an autoregulation of blood flow and pressure reduction to 100mmHg during acetylcholine infusion resulted in a marked increase of renin secretion without any further change in afferent arteriolar resistance. Intrarenal arterial infusion of norepinephrine at a control pressure increased a renin release. However, norepinephrine infusion at reduced pressure suppressed the renin release with recovery a vascular resistance to the control level. These results suggest that the changes in the degree of blood flow and pressure in the renal afferent arterioles are not essential for the renin release, but renin release by the pressure reduction might be related to the autoregulatory capacity of afferent arterioles in the outer cortex.

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