Long-term prehypertension treatment with losartan effectively prevents brain damage and stroke in stroke-prone spontaneously hypertensive rats

Abstract

Prehypertension has been associated with adverse cerebrovascular events and brain damage. The aims of this study were to investigate i) whether short- and long-term treatments with losartan or amlodipine for prehypertension were able to prevent blood pressure (BP)-linked brain damage, and ii) whether there is a difference in the effectiveness of treatment with losartan and amlodipine in protecting BP-linked brain damage. In the present study, prehypertensive treatment with losartan and amlodipine (6 and 16 weeks treatment with each drug) was performed on 4-week-old stroke-prone spontaneously hypertensive rats (SHRSP). The results showed that long-term (16 weeks) treatment with losartan is the most effective in lowering systolic blood pressure in the long term (up to 40 weeks follow-up). Additionally, compared with the amlodipine treatment groups, the short- and long-term losartan treatments protected SHRSP from stroke and improved their brains structurally and functionally more effectively, with the long-term treatment having more benefits. Mechanistically, the short- and long-term treatments with losartan reduced the activity of the local renin-angiotensin-aldosterone system (RAAS) in a time-dependent manner and more effectively than their respective counterpart amlodipine treatment group mainly by decreasing AT1R levels and increasing AT2R levels in the cerebral cortex. By contrast, the amlodipine treatment groups inhibited brain cell apoptosis more effectively as compared with the losartan treatment groups mainly through the suppression of local oxidative stress. Taken together, the results suggest that long-term losartan treatment for prehypertension effectively protects SHRSP from stroke-induced brain damage, and this protection is associated with reduced local RAAS activity than with brain cell apoptosis. Thus, the AT1R receptor blocker losartan is a good candidate drug that may be used in the clinic for long-term treatment on prehypertensive populations in order to prevent BP-linked brain damage.

Loss of the heterogeneous expression of flippase ATP11B leads to cerebral small vessel disease in a normotensive rat model

“…2b), and no difference between males and females. They are clearly different to the hypertensive SHRSP model rats at the same ages [25]. Varied expression of ATP11B immunogold labelling in neighbouring wildtype ECs in the same transverse section of a blood vessel.…”

Regulation of Hypertension for Secondary Prevention of Stroke: The Possible ‘Bridging Function' of Acupuncture

“…After stimulation of LI11, ST36, HT7, and LI15 for 30 min in SHRs, the plasma Ang II levels in the LI11, ST36, and HT7 groups and the aldosterone (ALD) levels in the ST36 and HT7 groups were lowered significantly, and the plasma atrial natriuretic peptide (ANP) content in the HT7 group increased obviously [88]. Inhibition of the renin-angiotensin-ALD system (RAAS) is associated with reduced stroke-induced brain damage [89], and ANP protects against cardiac remodeling [90]. …”

A Study on Effect of Electroacupuncture on Gene Expression in Hypothalamus of Rats with Stress-Induced Prehypertension Based on Gene Chip Technology

“…The study found that the incidence of cardiovascular events in the people with prehypertension in the future was two times as that of the people with normal blood pressure [ 8 ]. It is also proved that stress-induced hypertension is preceded by the damage of target organs like blood vessels [ 9 ], heart [ 10 ], brain [ 11 ], and kidneys [ 12 ] and changes of the expressions of relative proteins and genes. Therefore, early stage treatment could effectively reduce the incidence of high blood pressure and protect target organs.…”