Heritability of intracerebral hemorrhagic lesions and cerebral aneurysms in the rat

Background and Purpose-Under certain conditions, the Brown Norway (BN) rat is susceptible to intracerebral hemorrhagic vascular (ICV) lesions within t he cerebral cortex, whereas the Long-Evans (LE) rat is prone to develop ane urysms in the circle of Willis. The incidence of these 2 pathological pheno types was studied in progeny of different BNXLE crosses to determine their heritability in these new rat models. In addition, a possible link between ICV lesion occurrence and either the susceptibility to spontaneous rupture of the arterial internal elastic lamina (IEL) or basal plasma angiotensin-c onverting enzyme (ACE) activity was also studied in back-cross (BC) F1XBN r ats, the only second-generation group with a high incidence of ICV lesions. Methods-To induce cerebrovascular lesions, rats were submitted to experimen tal hypertension associated with ligation of 1 carotid artery. After death, the brain was examined for cerebral lesions. Numbers of arterial IEL ruptu res were determined microscopically with the use of en face preparations, p lasma ACE activity was determined before the induction of hypertension. Results-In general, groups that developed ICV lesions presented a low incid ence of aneurysms. ICV lesion incidence was similar in F1 hybrids and BC(F1 XBN) and greatly decreased in F2 and BC(F1XLE) rats compared with BN rats. No cerebral aneurysms developed in Fl rats. Aneurysmal incidence was 24% (2 0% ruptured) in LE, 42% (59% ruptured) in F2, and 50% (75% ruptured) in BC( F1XLE) rats. In BC(F1XBN) rats, neither the incidence of IEL rupture nor th e plasma ACE activity was higher in the rats with ICV lesions. However, the mean blood pressure level was higher in these rats, and peak blood pressur e was higher in rats with the most severe grades of ICV lesions. Conclusions-These data suggest a polygenic and dominant mode of inheritance of ICV pathology. The formation of aneurysms in the circle of Willis tende d to be favored, and their rupture was clearly increased by the presence of BN rat alleles within the LE rat genome. These data may provide the basis for future studies to determine, in new rat models, which genes are involve d in these pathologies.