Renovascular hypertension causes cerebral vascular remodeling

Renovascular hypertensive rats （RHRs） were developed using the 2-kidney, 2-clip method. All RHRs at 10 weeks displayed high permeability of the cerebral surface blood vessels. Vascular casts of the RHRs showed that the vascular network was sparse. The arterioles of the RHRs at 10 weeks had smaller lumen diameters, but thicker vessel walls with hyalinosis formation compared with control animals. The endothelial cell membrane appeared damaged, and microthrombus formed. After ischemia, the infarction size was larger in RHRs than in control animals. These results suggest that cerebral arterioles in RHRs underwent structural remodeling. High blood pressure may aggravate the severity of brain injury in cerebral ischemia and affect the recovery of ischemia.

Effect of prenatal tetrandrine therapy on pulmonary vascular structural remodeling in the nitrofen-induced CDH rat model

To examine the effects of prenatal tetrandrine (Tet) therapy on pulmonary arterial structural remodeling in nitrofen-induced congenital diaphragmatic hernia (CDH) Methods CDH was induced in fetal rats by maternal administration of 100*!mg nitrofen by gavage on day 9 5 of gestation (term, day 22) Control animals received olive oil (OO) Tet (24*!mg/kg per day) or normal saline (NS) was given by gavage every day from 16 to 20 days of gestation, and fetuses were delivered by caesarean section on day 21 5 Lung sections from 3 fetuses in each group were studied The number of vessels were calculated, the external diameter (ED), medial wall thickness (MT), percent of medial wall thickness, and wall structure were evaluated by image analysis software Results In the pre-acinar arteries, CDH-NS pups had a significantly increased %MT compared with the OO-NS group ( P <0 05), while CDH-Tet animals had a reduced %MT compared with the CDH-NS rats ( P <0 05) Similar results were seen in the intra-acinar level Significant differences were observed between CDH-NS animals and OO-NS controls in the percentage of muscularized intra-acinar blood vessels ( P <0 001) Tet-treated CDH pups had a reduced percentage of muscularized intra-acinar arteries compared with CDH-NS animals Conclusions Medial hypertrophy is present in both the pre-acinar and intra-acinar arteries in the nitrofen-induced CDH rat model Tet treatment inhibits medial hypertrophy and reduces the percentage of muscularized intra-acinar vessels Prenatal Tet therapy may be efficacious in reducing the risk of PH in human newborns with CDH

Effects of angiotensin Ⅱ receptor antagonist olmesartan on renal hemodynamic variables and vascular structural properties in streptozotocin-induced diabetic rats

Background Diabetic nephropathy is a major cause of renal failure in diabetes mellitus （DM）. It has been known that renin-angiotensin system （RAS） blockers have a renal protective effect. This study aimed to investigate whether treatment with angiotensin Ⅱ receptor blocker, olmesartan, could modify renal hemodynamic variables and vascular structural properties, then attenuate renal injury in streptozotocin （STZ）-induced DM rats.Methods DM was induced in male Wistar rats by intraperitoneal administration of STZ. The rats were then randomized to a DM group and an olmesartan treatment （OLM＋DM） group. The normal group （non-DM） were administered only citrate buffer. At the end of the 14th week, blood glucose, kidney weight/body weight and urinary protein-to-creatinine ratio were determined. Further, the flow-pressure and pressure-glomerular filtration rate （GFR） relationships were determined for maximally vasodilated, perfused kidneys. From the relationship, 3 indices of vascular structural properties were estimated： slope of flow-pressure （minimal renal vascular resistance, reflecting overall luminal dimensions of preglomerular and postglomerular vasculature）, slope of pressure-GFR （glomerular filtration capacity against pressure）and threshold pressure for beginning filtration at pressure-GFR （preglomerular to postglomerular vascular resistance ratio）. Kidneys were then perfusion fixed for histological analysis. The renal histopathology was observed by light microscopy.Results The body weight of DM rats was lower than that of non-DM rats. Blood glucose, kidney weight/body weight,urinary protein-to-creatinine ratio were significantly greater in DM rats than in non-DM rats. The parameters such as kidney weight/body weight, urinary protein-to-creatinine ratio in OLM＋DM rats had dramatically decreased compared with those in DM rats. However, the treatment with olmesartan had no effect on blood glucose levels. The slope of flow-pressure relationship was greater in DM rats than that in non-DM rats （P 〈0.05）. But the slope of the pressure-GFR relationship was lower in DM rats than that in non-DM rats （P 〈0.05） with the x-intercept of the line similar between the two groups. The slope of the flow-pressure relationship was decreased in DM rats group treated with olmesartan （P 〈0.05）. Moreover, olmesartan significantly increased the slope of the pressure-GFR relationship in DM rats （P 〈0.05）.The x-intercept of the pressure-GFR relationship reduced following olmesartan in DM rats.Conclusions Treatment with olmesartan reduced urinary protein-to-creatinine ratio independent of blood glucose and increased average renal vessel lumen diameter in the perfused kidneys of STZ-induced DM rats, predominantly in preglomerular vessels, and then improved renal excretory capability. These findings were consistent with remodeling of the preglomerular vasculature in our hisological measurements.

Qingxuan Jiangya Decoction(清眩降压汤) Prevents Blood Pressure Elevation and Ameliorates Vascular Structural Remodeling via Modulating TGF-β 1/Smad Pathway in Spontaneously Hypertensive Rats

Objective:To elevate the effects of Qingxuan Jiangya Decoction(清眩降压汤,QXJYD)on hypertension and vascular structural remodeling(VSR)in spontaneously hypertensive rats(SHRs),and investigate the underlying mechanisms.Methods:SHRs(n=8)were given intra-gastric administration with 60 mg/kg of QXJYD or saline,daily for 8 weeks,while rats in SHR-control(n=8)and WKY(n=8)groups were received equal volumes of saline solution.Systolic blood pressures(SBP),diastolic blood pressures(DBP)and mean blood pressures(MBP)were measured once a week.The levels of angiotensinⅡ(AngⅡ),endothelin 1(ET-1)and plasma renin activity(PRA)were tested by enzyme-linked immunosorbent assay(ELISA)and radioimmunoassay,respectively.The effect of QXJYD on VSR was determined by examining the media thickness and the ex vivo contractility of thoracic aortic.The proliferation and fibrosis of vascular smooth muscle cells(VSMCs)were examined via immunohistochemical(IHC)staining for proliferating cell nuclear antigen(PCNA),collagen Ⅰ and collagen Ⅲ,respectively.The mRNA and protein expressions of transforming growth factor β1(TGF-β1),Smad3 and phosphorylation of Smad3 in thoracic aorta tissues were determined by real-time polymerase chain reaction(PCR)and Western blot assay,respectively.Results:QXJYD treatment led to a significant decrease of the elevation of blood pressure in SHRs and reduced the levels of AngⅡ,ET-1 and PRA in the serum(P<0.05).In addition,QXJYD treatment remarkably ameliorated VSR and vascular function in SHRs.Moreover,QXJYD inhibited VSMC proliferation and fibrosis by suppressing the expression of PCNA,collagen Ⅰ and collagen Ⅲ in thoracic aortic.Furthermore,QXJYD inhibited the expression of TGF-β1,Smad3 and the phosphorylation of Smad3,respectively(P<0.05).Conclusion:QXJYD reversed VSR by inhibiting VSMC proliferation and collagen deposition via regulation of TGF-β1/Smad signaling pathway,which may,in part,illuminate its anti-hypertensive activities.