Bradykinin relaxation in small porcine retinal arterioles

Abstract

Purpose: To study changes in the spontaneous diameter of small retinal arterioles and bradykinin (BK)-induced vasodilation during inhibition of the synthesis of nitric oxide (NO), prostaglandins (PGs), and cytochrome P450 2C8/9-dependent endothelial-derived hyperpolarizing factor (EDHF).

Methods: Forty-eight isolated porcine arterioles with a diameter of approximately 70 microm were mounted in a double-barreled pipette system placed in an organ bath, and diameter changes were studied under isobaric conditions. After an equilibration period, the arterioles were incubated with inhibitors of the synthesis of NO, PGs, or cytochrome P450 2C8/9-dependent EDHF, and spontaneous diameter changes were studied. Subsequently, the arterioles were precontracted, and the diameter was assessed after addition of BK in cumulative concentrations.

Results: Inhibition of NOS elicited a significant decrease in the spontaneous diameter of the vessels (P = 0.028), whereas no change in the spontaneous diameter was induced by inhibition of PG or cytochrome P450 2C8/9 dependent EDHF synthesis (P = 0.35 and P = 0.75, respectively). The vasodilating effect of BK was decreased by inhibition of NO (P = 0.002) but not by inhibition of prostaglandin or cytochrome P450 2C8/9-dependent EDHF synthesis (P = 0.82 and P = 0.94, respectively).

Conclusions: The results suggest the presence of a spontaneous release of NO, which keeps the retinal microcirculation dilated under normal conditions. The finding of BK-induced relaxation being dependent on the NO synthase (NOS), but not on PGs or cytochrome P450 2C8/9-dependent EDHF may be of importance for understanding the microcirculatory effects of pharmacologic compounds affecting the BK metabolism, such as angiotensin-converting enzyme (ACE) inhibitors.