ENDOTHELIAL FACTORS AND AUTOREGULATION DURING PRESSURE CHANGES IN ISOLATED NEWBORN PIGLET CEREBRAL-ARTERIES

To analyze newborn cerebrovascular autoregulation, middle cerebral art eries from 3-4-d-old piglets were cannulated, and diameter changes aft er transmural pressure variation were measured. After an equilibration period at 30 mm Hg, pressure was modified from 10 to 70 mm Hg in 20-m m Hg steps. Segments with endothelium showed vasodilation during press ure decrease and vasoconstriction during pressure increase. In each ca se the maximum response was about 5% that of the resting diameter. Seg ments without endothelium responded passively to pressure change. Vaso dilation during pressure decrease was reduced by the preferential calc ium-activated potassium (K-Ca) channel blocker, tetraethylammonium (1 mM), and was absent with the nitric oxide (NO) synthase inhibitor NG-n itro-L-arginine methylester (L-NAME, 10 mu M). The NO synthase substra te, L-arginine (10 mu M), counteracted the dilation blockade caused by L-NAME. The cyclooxygenase inhibitor indomethacin (10 mu M) and the e ndothelin A receptor antagonist BQ-123 (10 mu M) eliminated the pressu re increase-induced vasoconstriction. The ATP-sensitive potassium chan nel blocker, glibenclamide (1 mu M), and the endothelin B receptor ant agonist, BQ-788 (10 nM), did not modify the autoregulatory response. N one of these drugs modified the passive changes produced by pressure v ariations in segments without endothelium. These results suggest that: 1) piglet middle cerebral artery autoregulation is endothelium-depend ent; 2) NO and K-Ca channels are involved in vasodilation during trans mural pressure decrease, and 3) endothelin-1, through endothelin A rec eptors, and prostanoids mediate vasoconstriction during pressure incre ase.