The Role of the Renin-Angiotensin and Cardiac Sympathetic Nervous Systems in the Development of Hypertension and Left Ventricular Hypertrophy in Spontaneously Hypertensive Rats.

Abstract

To elucidate the relationship between the development of left ventricular hypertrophy (LVH) in hypertension and the development of both the cardiac sympathetic nervous and renin-angiotensin systems, as measured by norepinephrine and angiotensin II levels, respectively. In this longitudinal study, we com- At 5 wk, systolic blood pressure was the same in both strains. But the left ventricular plus septum weight to body weight (LVSW/BW) ratio was higher in SHR than in WKY rats (p < 0.01), which finding may have been related to the increased cardiac tissue NE concentration, and this increase tended to parallel the rise in blood pressure. Both left ventricle and forelimb muscle NE concentrations were significantly higher in SHR than in WKY rats at 5, 10, and 15 wk of age (p < 0.01, respectively), and were similar at 20 and 28 wk of age. The heart and plasma Ang II levels decreased with age, which results were in keeping with the known developmental tendencies of the biological aging progress. There was no significant difference in plasma Ang II levels between the two strains from 5 to 20 wk, whereas these levels were remarkably higher in WKY than in SHR rats at 28 wk (p < 0.01 The Left ventricular hypertrophy (LVH) occurring in hypertension is known to be an independent risk factor for cardiovascular diseases. In addition to increased arterial pressure, such neurohormonal factors as norepinephrine (NE) and angiotensin II (Ang II) are well known to play important roles in the development of LVH. Although the mechanism for this effect is uncertain, NE and Ang II might promote cell hypertrophy by directly stimulating the synthesis of myocyte cell protein. It has been demonstrated the Sympathetic Nervous System (SNS) and Renin Angiotensin System (RAS) may contribute to the development of LVH and may be involved in the regression of LVH by antihypertensive drugs (1, 2), with the cardiac tissue RAS playing the more important role in this progression.Spontaneously hypertensive rats (SHR) have been studied by numerous investigators interested in their hypertension and cardiovascular hypertrophy, which are very similar to primary hypertension in humans. Imai (3) reported that an increase in a 1-adrenergic receptors might be involved in cardiac hypertrophy in the early phase of hypertension in SHR. Current evidences suggest that the SNS be important in the early stage of development of hypertension and LVH in SHR (4-8). It remains uncertain whether the SNS and RAS exert their influences on hypertension and LVH over the same age-span of SHR. In the present longitudinal study, we therefore compared blood pressure, left ventri-

Lisinopril Reduces Left Ventricular Hypertrophy and Cardiac Polyamine Concentrations without a Reduction in Left Ventricular Wall Stress in Transgenic Tsukuba Hypertensive Mice.

“…this concept continue to accumulate (48)(49)(50)(51). In our previous report (52), THMs showed blood and myocardial Ang II concentrations that were four to five times as high as those in C57BL16 mice.…”

Noninvasive Evaluation of the Time Course of Change in Cardiac Function in Spontaneously Hypertensive Rats by Echocardiography

“…Furthermore, Dang et al (16) showed that LV tissue angiotensin-II concentrations were significantly higher in SHR than in WKY from 15 to 28 weeks of age, although plasma angiotensin-II levels were similar in both groups. Angiotensin-converting enzyme activities in the SHR hearts may be important targets in terms of the ability of angiotensin-converting enzyme inhibitors to inhibit cardiac hypertrophy (17).…”

“…The main purpose of the present study was to perform a noninvasive evaluation of the time course of changes in car- 4,6,8,12,16,20 …”

β-Adrenergic Activation Initiates Chamber Dilatation in Concentric Hypertrophy

“…Although this finding does not affect the interpretation of our data (evaluations of the actions of ISO on WKY was not a primary goal of the present study), these data suggest that animals with LVH are more sensitive to the detrimental effects of chronic ␤-AR activation. As LV tissue noradrenaline and angiotensin II concentrations are reported to be increased in SHR compared with WKY, 30 it is likely that SHR are predisposed to cardiac remodeling. However, without more extensive studies with a longer duration of ISO administration, this hypothesis remains speculative.…”