The brain kallikrein-kinin system. A possible role in blood pressure regulation.

uring the last decade, the actions of central nervous system peptides on blood pressure and volume homeostasis have been the subject of intense investigation. There is evidence that central mechanisms of cardiovascular control could be modulated by brain peptides. Kinins are biologically active peptides released from kininogen by either glandular or plasma kallikrein. 1 Kinins in the central nervous system, released by glandular (tissue) kallikrein, may act at or near their site of origin. Components of the kallikrein-kinin system are found in a variety of tissues, among them the central nervous system. An enzyme that has the physical and chemical characteristics of glandular kallikrein has been identified in the rat brain. Kininogenase activity and immunoreactive glandular kallikrein have been shown to be similarly distributed within the brain. The presence of a messenger RNA (mRNA) coding for tissue kallikrein has been documented in both whole brain and discrete regions therein. 2 - 4 Thus, the presence of mRNA functionally able to direct kallikrein synthesis, immunoreactive kallikrein, and kinin-forming activity in the brain indicates that the kallikrein-kinin system is present there as well. The effects of a neuropeptide on the heart and blood pressure after central administration suggest a possible function of the endogenous system. Injec- tions of bradykinin into the intracerebral ventricles as well as discrete areas that include the hypothalamic nuclei increase blood pressure and heart rate. 5 By themselves, however, these data do not prove that the endogenous brain kallikrein-kinin system plays a role in modulating cardiovascular homeostasis. The recent availability of a competitive bradykinin receptor antagonist allows us to study the effects of blocking brain kinins on cardiovascular homeostasis. The work of Madeddu et al 6 provides evidence that under some experimental conditions, endogenous brain kinins are responsible for changes in blood pressure. It has been known for some time that spontaneously hypertensive rats (SHR) given central angiotensin converting enzyme inhibitor (CEI) respond with a transitory hypertensive response. 7