CONFOCAL MICROSCOPIC CHARACTERIZATION OF A LESION IN A CEREBRAL VESSEL OF THE STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RAT

Background and Purpose Hypertension is a major risk factor for stroke and is associated with alterations in vascular structure and function. The aim of this study was to determine vascular function, wall morpho logy, and vascular smooth muscle cell (VSMC) arrangement in basilar ar teries from stroke-prone spontaneously hypertensive rats (SHRSP) and n ormotensive control strain Wistar-Kyoto rats (WKY). The effect of peri ndopril treatment on SHRSP structure and function was also assessed. M ethods VSMC orientation was determined with laser-scanning confocal mi croscopy and computer-assisted image processing in basilar arteries st ained with 5(6)-carboxyfluorescein (wavelengths: excitation, 488; emis sion, 515) or propidium iodide (excitation, 529; emission, 550). Measu rements of wall morphology and functional responses to serotonin and K CI were assessed with wire myography. Results In the WKY basilar arter ies, VSMCs were uniformly oriented perpendicular to the longitudinal a xis of the vessel, whereas in the SHRSP them were localized foci of VS MC geometric disorganization, with a significant deviation from 90 deg rees. The SHRSP basilar arteries also showed structural remodeling and reduced contractile responses to serotonin and KCI. Perindopril treat ment normalized blood pressure, pre vented wall morphology alterations , and improved function but had no effect on VSMC disorganization. Con clusions This is the first demonstration of lesions of VSMC geometric disorganization in a cerebral artery from a stroke-prone genetically h ypertensive rat strain. These structural abnormalities are independent of blood pressure. Their functional sequel may play a role in the pat hogenesis of stroke in this model.