EFFECTS OF EXTRACELLULAR PH ON AGONIST-INDUCED VASCULAR TONE OF THE CAT OPHTHALMOCILIARY ARTERY

Purpose. To test whether changes in extracellular pH (pHe) in an in vi tro preparation of the cat ophthalmociliary artery affect passive tone and agonist responses and whether the endothelial cells are mediators of any pH-induced effect. This will determine the ability of the opht halmociliary artery to influence retinal and choroidal blood flow in r esponse to metabolic stimuli. Methods. The isometric tension generated by isolated ring segments preactivated by prostaglandin F-2 alpha (PG F(2 alpha)), noradrenaline (NA), or 40 mM K+ was measured as the pHe o f the bathing solution was changed stepwise from 6.0 to 8.0 by adjusti ng the bathing bicarbonate concentration in preparations with and with out functioning endothelial cells. Results. PGF(2 alpha) produces a co ncentration-dependent contraction that is insensitive to an alkaline s hift from control pHe (7.4) in the bathing medium. For acidic shifts t o pHe 7.0, there is no significant change in the magnitude of the PGF( 2 alpha) contraction, whereas at pHe 6.0, the PGF(2 alpha) contraction is reduced to 23 +/- 4% (n = 23) of its value at pHe 7.4. Threshold r esponse concentration remains unaffected. Deliberate damage to the end othelial cells does not significantly affect the magnitude of the 10(- 5) M PGF(2 alpha) response at pHe 7.4 nor the effect of acidic pH on t his response. The 10(-5) M NA response is reduced in a graded fashion to acidic shifts to pH 7.0 and 6.0 (40 +/- 4% [n = 23]) and also to al kaline shift to pH 8.0 (22 +/- 5% [n = 23]) when compared to the induc ed tension at pHe 7.4. For the acidic shift only, endothelial cell dam age causes a further significant reduction in the NA response to 20 +/ - 3% (n = 5). For vessels contracted with K+-Krebs solution, there is a small but significant reduction in response at pHe 6.0 to 84 +/- 6% (n = 25), whereas for pHe 8.0 there is a much larger reduction to 45 /-: 5% (n = 24). All pile-induced relaxations of K+ are endothelium in dependent. Passive tension is unaffected by all pHe manipulations. Con clusions. Vessel responses to vasoactive agents are selectively mediat ed by pHe changes. Major acidic shifts cause reduced responses (relaxa tion) to NA, PGF(2 alpha), or K+, whereas only vessels preactivated wi th NA and K+ relax to alkaline shifts. This implies that NA or K+ indu ced vascular responses are maximal close to neutral pHe with major shi fts from neutrality in either the acidic or alkaline direction causing a reduced response. These results imply that the ophthalmociliary art ery probably does not play a major role in controlling ocular blood ho w in response to pHe changes within the normal metabolic range, but it may became important in ischemic conditions.