Potentiation by hypoxia of contractions caused by angiotensin II in dog and monkey cerebral arteries.

Abstract

Background and Purpose: Hypoxia alters the responsiveness to endogenous substances of cerebral arteries, possibly resulting in the modulation of blood supply to ischemic brain regions. The present study was undertaken to analyze the mechanism of potentiation by hypoxia of angiotensin ll-induced cerebroarterial contractions.Methods: Monkey and dog cerebral arterial strips with endothelium were suspended for isometric tension recording in Ringer-Locke solution aerated with 95% 02-5% CO2 (partial 02 pressure, 570-600 mm Hg) or 95% N2-5% CO2 (approximately 10 mm Hg).Results: Contractions induced by angiotensin II and substance P were potentiated by exposure to hypoxia, whereas contractile responses to prostaglandin F2,, were not influenced. Treatment with cyclooxygenase inhibitors abolished the peptide-induced contraction but did not alter the prostaglandin F2a,-induced contraction. Relaxations induced by arachidonic acid were suppressed by indomethacin and hypoxia, whereas those caused by a prostaglandin I2 analogue were unaffected. Conclusions: The potentiation by hypoxia of cerebroarterial contractions caused by angiotensin II and substance P appears to be due to an interference with the synthesis of prostaglandin 12 from arachidonic acid and a resultant increase in the production of vasoconstrictor prostaglandins. (Stroke 1993;24:421-426 (9,11),(11,12)-dideoxa-9,11-dimethylmethano-11,12-methano-13,14-dihydro-13-azo-14 -oxo-15 -cyclopentyl-16,17,18,19,20 -pentanor-15 - Results Effect on Dog Cerebral ArteriesThe addition of Ang II in a concentration of 10`7 M produced a phasic contraction in dog cerebral arterial strips that was abolished by treatment with 10`' M saralasin or 10`6 M indomethacin (n =5), as shown in an earlier report.1 In the strips exposed for 15-20 minutes to the bathing media aerated with 95% N2-5% CO2, the contraction caused by Ang II was significantly increased (Figure 1). However, contractions associated with PGF2, in concentrations (2-5x10`M) producing a magnitude of contraction similar to that induced by Ang II were not significantly increased by exposure to severe hypoxia. Typical recordings of the response to the peptide and PGF2a under control and hypoxic conditions are illustrated in Figure 2. The PGE2 (3 x 10-7 M)-induced contraction was decreased by hypoxia from 285±44.6 to 117+18.8 mg (62.7+3.0% decrease, n=6, p<O.OOl). In the same strips, Ang lI-induced contractions were increased by 190+29.4% (n=6). As seen in normoxia, the contraction elicited by Ang II was markedly inhibited by indomethacin in hypoxic solutions (from 242±41 to 37+11 mg, n=4, 96.3+3.7% inhibition, p<O.OOl), whereas contractions induced by PGF2, and PGE2 were not altered.In circles) of a dog basilar arterial strip with endothelium that has been exposed to control media and hypoxic media in the absence or presence of indomethacin (10'6M).units/ml) did not alter the peptide-induced contraction under control conditions (n=6). Therefore, it seems unlikely that the increased production of oxygen radicals in control...