What's new in the cerebral microcirculation? Landis Award lecture

The first part of this paper focuses on unusual aspects of the cerebral circulation. Cerebral vessels have less smooth muscle and adventitia than other vessels, and the endothelial blood-brain barrier is unique. Because the wall of the arteries is thin, one might expect that the vessels are especially vulnerable to rupture. Pressure in intracranial arteries, however, is lower than in other arteries, because resistance of larger cerebral arteries is remarkably high. The low pressure in cerebral arteries presumably protects against rupture of the vessels. The second part of the paper summarizes some new insights into regulation of cerebral circulation. One concept is that "breakthrough" of autoregulation, with dilatation of cerebral vessels at high levels of pressure, is an active process, rather than a passive phenomenon. This conclusion is based on the finding that inhibitors of calcium-dependent potassium channels greatly attenuate the cerebral vasodilator response during acute hypertension. The third part of the paper focuses on effects of gene transfer to cerebral blood vessels. Gene transfer to intracranial and extracranial vessels is feasible and vasomotor function can be altered. Gene transfer has proven to be useful to study vascular biology, and we are optimistic that the approach will ultimately lead to gene therapy.