Previous studies have shown that the cerebral vasculature of adult (18-21 week old) spontaneously hypertensive rats (SHR) adapts to hypertension by hypertrophy of the vessel wall, resting vasoconstriction, and an upward shift in the systemic arterial pressure range for near-perfect autoregulation of blood flow. It is not presently known if cerebral vasuclar abnormalities progress gradually from the onset of hypertension or if they are present before blood pressure elevation occurs. Similarly, it is not known if the Goldblatt hypertensive rat (RHR) manifests cerebrovascular structure and function changes akin to those seen in age-matched SHR. Assuming that cerebrovascular abnormalities present in RHR and SHR are due primarily to elevations in blood pressure, the effects of blood pressure reduction by conventional oral antihypertensive drug therapy are largely unknown. It is not known if structural abnormalities in hypertensive cerebral vessels regress, arrest, or continue to evolve when blood pressure is pharmacologically reduced, or whether different sections of the vascular bed show divergent responses to antihypertensive therapy. Furthermore, the cerebrovascular consequences of the timing and duration of treatment are not known. Cerebrovascular parameters will be analyzed (relative to appropriate controls) in age-matched SHR and RHR at defined age intervals, with and without conventional antihypertensive therapy. Results obtained in untreated SHR and RHR will be compared to determine if these two types of hypertension exhibit similar effects on cerebral vascular structure and function. Additionally, responses to a variety of treatment schedules in each of the hypertensive models will be analyzed to determine the time-course and extent of reversibility of microvascular abnormalities. This research will provide a comprehensive longitudinal analysis of hypertensive cerebrovascular adaptations and their reversibility by drug treatment in two models of hypertension.
| Harper, S L (1987) Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats. Circ Res 60:229-37 |
| Harper, S L (1987) Effects of antihypertensive treatment on the cerebral microvasculature of spontaneously hypertensive rats. Stroke 18:450-6 |
| Harper, S L; Klevans, L R; Granger, D N (1987) Effects of the antihypertensive prostaglandin analog Ro 22-1327 on regional blood flows in the spontaneously hypertensive rat. J Cardiovasc Pharmacol 9:285-90 |
| Harper, S L; Pitts, V H; Granger, D N et al. (1986) Pancreatic tissue oxygenation during secretory stimulation. Am J Physiol 250:G316-22 |
| Harper, S L; Bohlen, H G; Granger, D N (1985) Vasoactive agents and the mesenteric microcirculation. Am J Physiol 249:G309-15 |
