The functional changes of the perivascular adipose tissue in spontaneously hypertensive rats and the effects of atorvastatin therapy.

The aim of this study was to examine the function of perivascular adiposa tissue (PVAT) on vascular relaxation response in spontaneously hypertensive rats (SHR) and the modulatory effects of the atorvastatin therapy on the PVAT functions. We investigated the mechanisms of the perivascular adipocyte-derived relaxation factor (PVRF) by using isolated rat's aortic rings and isometric contraction measurements. We found that contraction of the thoracic aorta induced by phenylephrine was significantly attenuated in the presence of PVAT from normotensive Wistar-Kyoto rats (WKY group) or the spontaneously hypertensive rats treated with atorvastatin (SHR-A group, atorvastatin 50mg/kg/day), whereas this effect was not observed in the thoracic aortic rings from the control SHR (SHR group). Transferring the solution incubated with PVAT-intact thoracic aorta to PVAT-free thoracic aorta, it induced a remarkable relaxation response in the WKY but not in the control SHR. Tetraethylammoniumchloride (TEA) could block the above relaxation. It was also shown that the PVRF function was likely, depending on the extracellular [Ca(2+)]; the anti-contractile effect of PVAT could be reduced by the inhibitor of the adenosine triphosphate (ATP)-dependent potassium channels, glibenclamide, and could be reduced by the inhibitor of cyclooxygenase by indomethacin. We thus infer that the PVAT function was distorted in hypertension rats, and the lipid-lowering treatment with atorvastatin could restore the PVAT function. The function of the PVRF may involve the Ca(2+)-activated potassium channels, the ATP-dependent potassium channels in vascular smooth muscle cell (SMC), and the release of PVRF from PVAT may involve prostaglandins (PGs) and the calcium metabolism. These results provide an insight into the pathological mechanisms of hypertension development, and indicate that the PVAT may be a potential new target for the hypertensive therapy.

Control of vascular changes by renin-angiotensin-aldosterone system in salt-sensitive hypertension.

The purpose of this study was to investigate the role of the renin-angiotensin-aldosterone system in hypertension development and cardiovascular structural changes in a salt-sensitive hypertensive model induced by capsaicin (CAP). Newborn male Wistar rats were injected with either capsaicin or vehicle. After weaning at 3 weeks, these rats were divided into the following six treatment groups: capsaicin plus high-salt diet (CAP+HS), control plus high-salt diet (CON+HS), control plus normal salt diet (CON+NS), capsaicin plus high-salt diet and telmisartan (CAP+HS+T, 10 mg/kg/day), capsaicin plus high-salt diet and perindopril (CAP+HS+P, 2 mg/kg/day), and capsaicin plus high-salt diet and spironolactone (CAP+HS+S, 80 mg/kg/day). Treatment with different salt diets and drugs was initiated at 3 weeks of age and lasted 18 weeks. We found that beginning at the second week after the initiation of the treatment, blood pressure became significantly higher in CAP+HS than in other groups, accompanied by the development of cardiac hypertrophy. Treatment with telmisartan, perindopril or spironolactone prevented the development of hypertension in the CAP+HS group. Cardiac hypertrophy was prevented in the perindopril treatment group. The medial thickness, media-to-lumen ratio and cross-sectional area of the thoracic, renal and mesenteric arteries were significantly increased in CAP+HS than in other groups. Lumen diameter was similar in all the vessels among all the groups. Treatment with telmisartan, perindopril or spironolactone prevented the development of vascular remodeling, as found in the CAP+HS group. Beginning at 8 weeks after the initiation of the salt diet treatment (11 weeks of age), blood pressure also became higher in CON+HS than in CON+NS, but lower than CAP+HS. Structural changes of vessels were also present in CON+HS, but the degree of change was less when compared with CAP+HS. We conclude that neonatal treatment with capsaicin plus a high-salt diet, and a high-salt diet alone both induced hypertension development in normal Wistar rats, which are associated with cardiovascular remodeling. The renin-angiotensin-aldosterone system is involved in this salt-sensitive model because treatment that interfered with this system also prevented the development of hypertension and vascular remodeling.

Arterial structural changes in hypertensive rats induced by capsaicin and salt loading.

1. The objective of the present study was to investigate the arterial structural changes in a salt-sensitive hypertensive rat model induced by treatment with capsaicin. 2. Newborn male Wistar rats were treated with 50 mg/kg capsaicin subcutaneously for 2 days. Control rats were treated with vehicle solution (5% ethanol and 5% Tween 80 in saline). After weaning at 3 weeks, rats were divided into four groups: (i) control with a normal salt diet (0.5% NaCl; CON + NS); (ii) control with a high-salt diet (4% NaCl; CON + HS); (iii) capsaicin plus normal salt diet (CAP + NS); and (iv) capsaicin plus a high-salt diet (CAP + HS). Treatment with different salt diets was initiated at 3 weeks of age and lasted for 18 weeks. Tail-cuff systolic blood pressure (BP) and bodyweight were examined. At the end of the treatment period, blood vessels were prepared by perfusion fixation. Heart weight and vascular dimensions were measured in the thoracic (artery) aorta, renal artery and mesenteric artery. 3. Two weeks after the initiation of the salt diet treatment, BP became significantly higher in the CAP + HS group than in any of the other groups and this difference was maintained until the end of the treatment period. 4. Beginning at 8 weeks after the initiation of the salt diet treatment (11 weeks of age), BP became higher in the CON + HS group than in the CON + NS and CAP + NS groups. Blood pressure was not significantly different between the CON + NS and CAP + NS groups. 5. Media thickness, media thickness to lumen ratio and cross-sectional area of the aorta, renal artery and mesenteric artery were significantly increased in the CAP + HS group compared with the other groups. Heart weight was also increased in the CAP + HS and CON + HS groups compared with the other groups. 6. Similar structural changes in the blood vessels and heart were also found in the CON + HS group compared with the CON + NS group. Lumen diameter was not altered by the treatments in any of the arteries studied. 7. We conclude that treatment with capsaicin increased the sensitivity of the BP of these rats to salt and this increase in BP is correlated with hypertrophy of the arteries (vascular remodelling) with no change in lumen size. A long-term high-sodium load induced hypertension in normal Wistar rats, which was accompanied by cardiovascular hypertrophy.