A substantial number of rat models have been used to research subarachnoid hemorrhage-induced cerebral vasospasm; however, controversy exists regarding which method of selection is appropriate for this species. This study was designed to provide extensive information about the three most popular subarachnoid hemorrhage rat models: the endovascular puncture model, the single-hemorrhage model, and the double-hemorrhage model. In this study, the basilar artery and posterior communicating artery were chosen for histopathological examination and morphometric analysis. Both the endovascular puncture model and single-hemorrhage model developed significant degrees of vasospasm, which were less severe when compared with the double-hemorrhage model. The endovascular puncture model and double-hemorrhage model both developed more vasospasms in the posterior communicating artery than in the basilar artery. The endovascular puncture model has a markedly high mortality rate and high variability in bleeding volume. Overall, the present study showed that the double-hemorrhage model in rats is a more suitable tool with which to investigate mechanism and therapeutic approaches because it accurately correlates with the time courses for vasospasm in humans.vasospasm; rat; models; subarachnoid hemorrhage
Abstract-The aim of this study was to examme the role of endothehn-A (ET,) receptors m mediating the hypertension and renal qury associated with high salt intake m Dahl salt-sensltlve (DS) rats To achieve this goal, we examined the effects of chronic selective ETA antagonist (A-127722) treatment at a dose of 10 mg/kg/d on arterial pressure, renal function, and morphology m DS and Dahl salt-reslstant (DR) rats placed on a high sodmm (8% NaCl) diet (HSD) for 3 weeks Placement of DS rats (n=l3) on HSD for 3 weeks caused a progressive increase m systolic pressure (from 118 +3 to 1862 15 mm Hg) The mcrease m systohc pressure was slgmficantly attenuated (from 125+4 to 167t 12 mm Hg) m DS rats treated with A-127722 (n= 13) Mean arterial pressure (MAP) measured directly at the end of the study was also slgmficantly lower by 18 mm Hg (P< 02) m the DS rats treated with A-127722The slope of the chronic pressure-natnuresls curve was shlfted to the right m DS rats and to the left by chronic ETA receptor blockade m DS rats The hypertension m DS rats was associated with marked protemurla (from 4 I+ 1 1 to 74 3t-5 3 mg/24 h/l00 g body weight) that was slgmficantly attenuated (from 5 721 2 to 55 226 5 mg/24 h/100 g body weight) m DS rats treated with A-127722The percentage of glomeruh dlsplaymg fibrons, hypercellulanty, and hyalmlzatlon was also slgmficantly reduced after treatment with A-127722 m DS rats Arterial pressure, protein excretion, renal hemodynanucs, and morphologc structure were not slgmficandy changed m response to ETA receptor blockade m DR rats placed on HSD These data indicate that endothehn-A receptor actlvatlon may play a role m the exacerbation of hypertension and development of renal injury m DS rats (Hy2lertension.1998;31[part 2]:397-402.)Key Words: endothehn receptors n kidney H rats # Dahl n hypertension E ndothehn-1 (ET-l) exerts a vanety of actions within the kidney that, If sustained chronically, could contribute to the development of hypertension and progresswe renal mJury ' ET-l causes a dose-dependent decrease m glomerular filtration rate (GFR) and renal plasma flow (RPF) through stlmulatlon of vascular smooth muscle and mesanglal cell contraction 23 Long-term effects of ET on the kidney include stlmulatlon of mesanglal cell prohferatlon and extracellular matnx deposmon as well as stlmulatlon of vascular smooth muscle hypertrophy m renal resistance vessels ' 4 Previous studies have indicated that expression of ET 1s greatly enhanced m ammal models of severe hypertension with renal vascular hypertrophy5" and m models of progressive renal qury " In addition, treatment with endothehn receptor antagonists attenuated the hypertension and small artery morphologc changes and improved kidney function m these models 9-'2 Dahl salt-sensltlve (DS) rats placed on a high sodium diet (HSD) are characterized by an attenuated pressure natnuresls, development of hypertenslon, and extensive renal lesions m the form of glomerulosclerosls, renal artenolar and tubular qury, and progresswe renal failure m late phases o...
While the rat has been used extensively in subarachnoid hemorrhage (SAH)-cerebral vasospasm studies, concerns exist whether this animal represents a usable model because its time course and pattern of cerebral vasospasm following SAH is not comparable to that observed in man. At present, our knowledge of the rat model is based almost exclusively on studies using a 'single hemorrhage' method. Since there is a positive correlation between severity of cerebral vasospasm, and volume of subarachnoid blood, an obvious question is whether the rat will show modifications in vascular responses when insulted by a second SAH. Here, an SAH was produced in rats using a 'double hemorrhage' method. Following SAH, cerebral arteries showed pathological alterations, significant decreases in luminal perimeter, and increases in arterial wall thickness, over a 7-day post-SAH period. The above vascular features are considered to be indicative of cerebral vasospasm and their presence over a 7-day post-SAH period represents a significant time extension when compared to a single hemorrhage. These modified vascular responses made the double hemorrhaged rat a much-improved animal model.
Histological, histochemical, and histoimmunological studies were conducted on cerebral arteries from three living patients with a recent subarachnoid hemorrhage. There seemed to be a correlation between the severity of vasospasm and the magnitude of pathological alterations. Myofibroblasts and Type V collagen within the medial layer were abundant in vessels showing marked constriction, but were less conspicuous in those arteries showing milder involvement. Intracranial arteries from patients who died from noncerebral causes did not demonstrate these changes. Thus, myofibroblasts and Type V collagen may be related to cerebral vasospasm by holding the damaged vessel in a contracted phase for weeks during the healing period.
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