Effects of clonidine on cerebral blood flow and the response to arterial CO2.
CBF, as measured by the clearance of 133Xe or 85Kr in the pentobarbital-anesthetized cat, displays a monotonic increase as the PaCO2 is elevated over a range of 20-60 mm Hg (slope Xe, 1.65 +/- 0.14 ml/100g/min/mm Hg; slope Kr, 1.40 +/- 0.11 ml/100 g/min/mm Hg). Clonidine (20 micrograms/kg i.v.), a centrally acting, alpha 2-preferring agonist, reduced the slope of the PaCO2-CBF response functions for Xe and Kr by 70 and 64%, respectively. Clonidine reduced normocarbic CBF-Xe by 36%, but had no effect on normocarbic CBF-Kr. ST-91, a polar structural analog of clonidine that does not cross the blood-brain barrier, did not reproduce the effects of clonidine when administered at an equivalent dose. This indicates that the effects of clonidine observed were secondary to its action on central rather than peripheral sites. In addition to the effects on the clearance of CBF markers, clonidine reduced the increased MABP otherwise evoked by elevated PaCO2. Reduction in the MABP response to PaCO2 did not account for the lowering of CBF during hypercarbia. In separate experiments where MABP was elevated to correspond with the PaCO2-MABP response observed in the absence of clonidine, a comparable reduction in the slope of the PaCO2 response was also observed. In addition, the pressure autoregulatory response was unaltered after clonidine treatment. These observations suggest that the central action of alpha 2-receptors on the CBF-CO2 response cannot be attributed to an altered perfusion pressure.
D000818:Animals; D001158:Arteries; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood*; D002415:Cats; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D005260:Female; D007726:Krypton; D008297:Male; D010841:Pia Mater / Q000098:blood supply; D011868:Radioisotopes; D011942:Receptors, Adrenergic, alpha / Q000502:physiology; D014980:Xenon Radioisotopes
D011868:Radioisotopes; D011942:Receptors, Adrenergic, alpha; D014980:Xenon Radioisotopes; D002245:Carbon Dioxide; D007726:Krypton; D003000:Clonidine