Rupture of the internal elastic lamina and vascular fragility in stroke-prone spontaneously hypertensive rats.

Abstract

We studied a possible relation between stroke and an enhanced susceptibility to rupture of the arterial internal elastic lamina by comparing stroke-prone spontaneously hypertensive rats with spontaneously hypertensive rats, which have a very low incidence of stroke. We quantified interruptions in the internal elastic lamina in certain arteries and studied the effect of -aminopropionitrile, an inhibitor of cross-link formation in collagen and elastic fibers, on rupture of the internal elastic lamina and on mortality in these two substrains. To eliminate any influence of higher blood pressure in the stroke-prone rats on the parameters studied, we used antihypertensive treatment to obtain equivalent blood pressures in the two substrains. Results showed that stroke sensitivity was associated with an enhanced early spontaneous rupture of the internal elastic lamina in the caudal artery, an increased susceptibility to /J-aminopropionitrile-induced rupture of the internal elastic lamina, and earlier mortality, mainly from aortic rupture, under /3-aminopropionitrile treatment These findings suggest that stroke-prone rats have an enhanced minor connective tissue defect that is expressed by rupture of the internal elastic lamina and may be related, at least in part, to their greater vascular fragility and increased susceptibility to stroke. (Stroke 1991^2:510-515) S pontaneously hypertensive rats of the strokeprone substrain (SHRSP) have been shown to be susceptible to the early development of cerebral vascular lesions 1 and are largely considered as a good model for stroke in humans.2 This substrain was established from the strain of spontaneously hypertensive rats (SHR). Although the severe hypertension and its rapid onset have been shown to be determinant in the occurrence of stroke in SHRSP, 3

Hemorrhagic Transformation during Thrombolytic Therapy and Reperfusion: Effects of Age, Blood Pressure, and Matrix Metalloproteinases

“…Stroke-prone SHRs develop a microangiopathy that resembles that of aged humans with chronic hypertension. 24,25 These rats will develop infarction and HT in 100% of aged subjects if fed a high-salt diet. 23 The mechanism of HT in these rats is not known.…”

Protection of the Arterial Internal Elastic Lamina by Inhibition of the Renin-Angiotensin System in the Rat

“…[1][2][3] The formation of IIEL is influenced by many factors, including age, 1 sex, 1,4 and hemodynamic factors such as blood pressure 1,2 and flow. 4,5 Although it appears that local factors determine IEL rupture within different arteries of any one rat, the overall susceptibility to this lesion is genetically determined.…”

Mechanisms Underlying Arterial Fragility and the Complications of Atherosclerosis

“…They occur spontaneously in other animals. Genetics, hypertension, connective tissue disorders (lathyrism) and hyperkinetic flow potentiate their development [26,[39][40][41], In humans they com mence in late fetal life or early infancy being found in all children 1-16 years of age. Early calcification commences in the tear margins and extends into the lamina [3].…”

“…Later they involve other arter ies and may be responsible for transverse intimal rippling of the aorta [2], IEL tears in the common and internal iliac arteries supplying a single umbilical artery predispose to overt atherosclerosis in the floor of the tears within 3 years of birth [3]. A propensity for stroke in spontaneously genetic hypertensive rats was correlated with frequent, early IEL tears [41],…”