This study assessed the protective effects of Rg1 on hypertension target-organ damage in SHRs. The main findings are as follows: (i) Rg1 attenuated the outward remodeling of aorta. (ii) Rg1 decreased the inward remodeling of small artery. (iii) Rg1 improved the cardial hypertrophy and fibrosis. (iv) Rg1 maintained the normal structure of kidney.
Numerous studies have demonstrated that high salt intake causes adverse structural and functional effects in the cardiovascular system [20, 21]. Excessive salt intake is often associated with an increase in arterial pressure and, consequently, increases in arterial pressure may partially mediate salt-related adverse effects . In addition to the well-admitted effect of sodium on blood pressure, several clinical and experimental observations are in favour of non-pressure-related effects of salt that could contribute to its influence on cardiovascular outcome . High salt intake caused hypertrophic response, then concentric cardiac-remodeling . High dietary salt led to widespread fibrosis and increased TGF-β1 in the heart and kidney in normotensive and hypertensive rats, suggesting that excessive salt intake may be an important direct pathogenic factor for cardiovascular disease .
Up to now, cardiovascular disease is still the most important factor that affects people’s life, especially the hypertension [1, 2, 25]. To delay or prevent hypertension target-organ, containing heart failure and renal failure, is essential to improve patient’s quality of life . In agreement with previous reports that the most common change found in large arteries in hypertension is an “outward hypertrophic remodeling”, we detected the increased lumen diameter and wall thickness in SHR compared with WKY. In hypertensive large arteries, these changes appear to be the consequence of cellular hypertrophy, cell hyperplasia, increased deposition of fibrillar or nonfibrillar matrix, or from a combination of these events [27–30]. Remodeling of the small resistance arteries may involve an inward or an outward remodeling [19, 31]. In the present study, we confirmed an inward remodeling in small retinal arteries of SHR compared with WKY. Rg1 treatment not only reduced the outward remodeling of large conductance arteries but also attenuated the inward remodeling of small resistance arteries, although no regulation of Rg1 on blood pressure was found. These results agree with those of other reports that ACE inhibitors are effective in controlling or reversing vascular remodeling, not depending on the anti-hypertensive effects [32, 33].
The final goal of novel therapy of hypertension is not only to normalize the blood pressure level but also to prevent end-organ damage, such as cardiac hypertrophy and renal dysfunction [26, 34]. Altered retinal arteries diameter has also been demonstrated to be associated with heart failure, suggesting that evaluation of the retinal microvasculature may be a useful predictor of target organ damage [35, 36]. Collagen deposition is the risk factor which plays an important role in development of organ failure, such as heart failure and renal failure . The myocardial matrix becomes less distensible, as the formation of the adducts in collagen resists normal turnover. Therefore, monitoring cardiac fibrosis and use of medicines that reverse collagen accumulation might represent a novel opportunity to alter the natural history of hypertensive heart disease.
In the previous report, the presence of myocardial hypertrophy and fibrosis in SHR was obvious at early stage, but the diastolic and systolic dysfunction did not occur until 13 to 18 months of age of SHR . This finding is in consistence with our present study. It is hopeful that the improvement of Rg1 on cardiac function could be detected by elongation of Rg1 treatment or selection of SHR more than 13 month old, basing on the anti-fibrotic effects of Rg1 at the early stage of hypertension.
We detected heart rate on conscious SHR during the experiment using tail-cuff apparatus, and up-regulation of Rg1 on heart rate was found. Increase of heart rate induced by Rg1 should be considered as a side effect in cardiovascular disease. Shen et al. have reported that Rg1 down-regulated heart rate in anesthetized mice treated by glutamate . The difference between our report and Shen et al. maybe derive from the different species used, suggesting the increase of Rg1 on heart rate may not occur if animal model other than SHR was used. Different biological response induced by extract from herbs between species was also reported [40, 41]. Further study was necessary to clarify the effects of Rg1 on heart rate on different species and the underlying mechanism.