Pathogenesis and Prevention of Stroke in Spontaneously Hypertensive Rats

1974 ◽  
Vol 48 (s2) ◽  
pp. 161s-163s ◽  
Author(s):  
K. Okamoto ◽  
F. Hazama ◽  
Y. Yamori ◽  
H. Haebara ◽  
A. Nagaoka
Keyword(s):  
Vascular Permeability ◽  
Spontaneously Hypertensive Rats ◽  
Selective Breeding ◽  
Severe Hypertension ◽  
Humoral Factor ◽  
Early Age ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Local Factors ◽  
Hypertensive Therapy

1. A colony of stroke-prone spontaneously hypertensive rats has been developed by selective breeding. 2. These animals developed severe hypertension early in life, the magnitude of the hypertension being closely related to the incidence of stroke. 3. No evidence was obtained of any humoral factor responsible for strokes. 4. Local factors predisposing to stroke were a scanty arterial supply with characteristic recurrent branching of long and large arteries, together with increased vascular permeability, angio-necrosis, and formation of microaneurysms. 5. Strokes could be prevented by adequate anti-hypertensive therapy from an early age.

Angiotensin-(1–7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with l-NAME

2006 ◽  
Vol 290 (2) ◽  
pp. H684-H691 ◽  
Author(s):  
Ibrahim F. Benter ◽  
Mariam H. M. Yousif ◽  
J. T. Anim ◽  
C. Cojocel ◽  
D. I. Diz
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rats ◽  
Severe Hypertension ◽  
Organ Damage ◽  
Left Ventricular ◽  
Protective Effects ◽  
Additive Effects ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
End Organ Damage

We examined the influence of chronic treatment with ANG-(1–7) on development of hypertension and end-organ damage in spontaneously hypertensive rats (SHR) chronically treated with the nitric oxide synthesis inhibitor l-NAME (SHR-l-NAME). l-NAME administered orally (80 mg/l) for 4 wk significantly elevated mean arterial pressure (MAP) compared with SHR controls drinking regular water (269 ± 10 vs. 196 ± 6 mmHg). ANG-(1–7) (24 μg·kg−1·h−1) or captopril (300 mg/l) significantly attenuated the elevation in MAP due to l-NAME (213 ± 7 and 228 ± 8 mmHg, respectively), and ANG-(1–7) + captopril completely reversed the l-NAME-dependent increase in MAP (193 ± 5 mmHg). l-NAME-induced increases in urinary protein were significantly lower in ANG-(1–7)-treated animals (226 ± 6 vs. 145 ± 12 mg/day). Captopril was more effective (96 ± 12 mg/day), and there was no additional effect of captopril + ANG-(1–7) (87 ± 5 mg/day). The abnormal vascular responsiveness to endothelin-1, carbachol, and sodium nitroprusside in perfused mesenteric vascular bed of SHR-l-NAME was improved by ANG-(1–7) or captopril, with no additive effect of ANG-(1–7) + captopril. In isolated perfused hearts, recovery of left ventricular function from 40 min of global ischemia was significantly better in ANG-(1–7)- or captopril-treated SHR-l-NAME, with additive effects of combined treatment. The beneficial effects of ANG-(1–7) on MAP and cardiac function were inhibited when indomethacin was administered with ANG-(1–7), but indomethacin did not reverse the protective effects on proteinuria or vascular reactivity. The protective effects of the ANG-(1–7) analog AVE-0991 were qualitatively comparable to those of ANG-(1–7) but were not improved over those of captopril alone. Thus, during reduced nitric oxide availability, ANG-(1–7) attenuates development of severe hypertension and end-organ damage; prostaglandins participate in the MAP-lowering and cardioprotective effects of ANG-(1–7); and additive effects of captopril + ANG-(1–7) on MAP, but not proteinuria or endothelial function, suggest common, as well as different, mechanisms of action for the two treatments. Together, the results provide further evidence of a role for ANG-(1–7) in protective effects of angiotensin-converting enzyme inhibition and suggest dissociation of factors influencing MAP and those influencing end-organ damage.

scholarly journals Nox (NADPH Oxidase) 1, Nox4, and Nox5 Promote Vascular Permeability and Neovascularization in Retinopathy

Hypertension ◽  
2020 ◽  
Vol 75 (4) ◽  
pp. 1091-1101 ◽  
Author(s):  
Devy Deliyanti ◽  
Saeed F. Alrashdi ◽  
Rhian M. Touyz ◽  
Christopher R. Kennedy ◽  
Jay C. Jha ◽  
...  
Keyword(s):  
Diabetic Retinopathy ◽  
Vascular Permeability ◽  
Spontaneously Hypertensive Rats ◽  
Inflammatory Factors ◽  
Vascular Endothelial ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Oxygen Induced Retinopathy ◽  
Vascular Endothelial Cadherin ◽  
Wistar Kyoto

Hypertension is a risk factor for the vascular permeability and neovascularization that threatens vision in diabetic retinopathy. Excess reactive oxygen species derived from the Nox (NADPH oxidase) isoforms, Nox1 and Nox4, contributes to vasculopathy in diabetic retinopathy; however, if Nox1/4 inhibition is beneficial in hypertensive diabetic retinopathy is unknown. Here, we determined that diabetic spontaneously hypertensive rats had exacerbated retinal vascular permeability and expression of angiogenic and inflammatory factors, compared with normotensive diabetic Wistar Kyoto rats. GKT136901, a specific dual inhibitor of Nox1 and Nox4, prevented these events in diabetic Wistar Kyoto rats and spontaneously hypertensive rats. Retinal neovascularization does not develop in diabetic rodents, and therefore, the oxygen-induced retinopathy model is used to evaluate this pathology. We previously demonstrated that Nox1/4 inhibition reduced retinal neovascularization in oxygen-induced retinopathy. However, although Nox5 is expressed in human retina, its contribution to retinopathy has not been studied in vivo, largely due to its absence from the rodent genome. We generated transgenic mice with inducible human Nox5 expressed in endothelial cells (vascular endothelial-cadherin + Nox5 + mice). In vascular endothelial-cadherin + Nox5 + mice with oxygen-induced retinopathy, retinal vascular permeability and neovascularization, as well as the expression of angiogenic and inflammatory factors, were increased compared with wild-type littermates. In bovine retinal endothelial cells, which express Nox1, Nox4, and Nox5, Nox1/4 inhibition, as well as Nox5 silencing RNA, reduced the high glucose–induced upregulation of oxidative stress, angiogenic, and inflammatory factors. Collectively, these data indicate the potential of Nox1, Nox4, and Nox5 inhibition to reduce vision-threatening damage to the retinal vasculature.

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