Proceedings of The Physiological Society
University of Oxford (2011) Proc Physiol Soc 23, PC132
Is cerebral blood flow a determinant of a long term arterial pressure set-point in the rat?
J. Paton1, S. Guild2, S. Malpas2, C. Barrett2
1. University of Bristol, Bristol, United Kingdom. 2. University of Auckland, Auckland, New Zealand.
Cushing (1901) discovered that acute increases in cerebral vascular resistance produced rises in arterial pressure. Subsequently, Dickinson and Thompson (1960) discovered that antemortem blood pressure correlated with a narrowing of the vertebral arteries such that hypertensive subjects had stenosed vessels; carotid and renal arteries did not show this correlation to be so strong. An explanation advanced by these authors was that restricted blood-carrying capacity of the vertebral arteries caused high blood pressure, but the issue of causality has remained controversial ever since. In the present, study we have sought to determine what effect reducing cerebral flow has on the chronic regulation of arterial pressure in the normotensive rat. All procedures were approved by the University of Auckland ethics committee. Under deep Halothane anaesthesia (3%; assessed by absence of pinch reflex to paw or the tail) Wistar rats were implanted with telemeters (Telemetry Research Ltd) for measuring arterial blood pressure chronically. Basal levels were monitored for 9 days prior to occlusion of both vertebral arteries, or both vertebral arteries plus a common carotid artery or both vertebral arteries, a common carotid artery and a common carotid artery clip to reduce blood flow. In rats in which common carotid arteries were ligated or partially occluded, the carotid sinus baroreceptors were denervated (under Halothane anaesthesia as above). Arterial pressure was monitored for up to 4 weeks. Bilateral occlusion of vertebral arteries alone was without effect on systolic blood pressure (SBP) or heart rate (n=3). In contrast, SBP was elevated in rats in which either both vertebral arteries plus a common carotid artery were occluded or occlusion of vertebral arteries, a common carotid artery and clipping the remaining common carotid artery. There was no difference in the pressor effect between these two latter groups which comprised an initial rise of 15±2 mmHg (mean±SEM; n=5, P<0.05 t-test). Over the following week there was a gradual and partial return towards control levels but a pressor effect remained above control levels (5±0.5 mmHg) that persisted for >20 days. In addition, the diurnal variability of blood pressure was enhanced. Post hoc analysis of the cerebral circulation indicated marked compensation including dilatation of the posterior communicating arteries and ventral spinal arteries feeding into the vertebrobasilar circulation. These studies provide the first proof of principle that reductions in cerebral blood flow can elevate arterial pressure chronically. Our findings are consistent with the notion of an intracranial baroreceptor (Rodbard & Stone, 1955). Our data also indicate that there is an impressive ability to compensate for reduced cerebral flow by recruitment from arteries in the spinal cord.
Where applicable, experiments conform with Society ethical requirements