Effects of cyclooxygenase inhibition on vascular responses evoked in fingers of men and women by iontophoresis of α1- and α2-adrenoceptor agonists

Abstract

Non-technical summary Sympathetic nerve fibres in the fingers release noradrenaline, which has the potential to act on α1- or α2-adrenoreceptors on the blood vessels. We used iontophoresis, which generates a tiny electrical charge, to push selective α1- or α2-receptor agonists through the skin and recorded changes in finger blood flow before and after aspirin, which inhibits cyclooxygenase (COX), an enzyme which synthesises vasodilator and vasoconstrictor prostaglandins. Our results yielded the novel findings that finger vasoconstriction produced by α1-adrenoceptors is blunted by locally synthesised vasodilator COX products in young men and in young women in the high but not the low oestrogen phase of the menstrual cycle. By contrast, finger vasoconstriction evoked by α2-adrenoceptors is largely attributable to vasoconstrictor COX products in young men, but overcome by vasodilator COX products in young women. This provides a foundation for testing whether COX products similarly modify vasoconstriction evoked by changes in sympathetic nerve activity. In 10 men and nine women aged 20-23 years, we aimed to establish whether endogenous prostanoids synthesised by cyclooxygenase (COX) affect responses evoked in the finger by α1- or α2-adrenoceptor agonists. Cutaneous red cell flux (cRCF) was recorded in dorsal finger during iontophoresis of phenylephrine (PE) or clonidine (0.5 mm, seven 0.1 mA pulses followed by one 0.2 mA pulse: 30 s each at 60 s intervals) before and after the COX inhibitor aspirin (600 mg p.o.). In men, PE evoked a biphasic mean increase/decrease in cRCF before but a monophasic mean decrease in cRCF of 30-40% after aspirin (P < 0.05). In women in the low oestrogen (E2) phase of the menstrual cycle, PE evoked a decrease in cRCF (30-40%; P < 0.05) that was unchanged by aspirin, whereas in the high E2 phase, PE evoked no change before but a graded decrease in cRCF (30-40%; P < 0.05) after aspirin. Clonidine evoked a decrease in cRCF (~30%; P < 0.05) in men before, but not after, aspirin. Clonidine evoked both increases and decreases in cRCF before and after aspirin in women in the low and high E2 phases (P > 0.05). We propose that finger vasoconstriction evoked by extraluminal α1-adrenoceptor stimulation is blunted by vasodilator COX products in young men and overcome by their action in women in the high, but not low E2, phase of the menstrual cycle. By contrast, α2-adrenoceptor stimulation evokes finger vasoconstriction that is mediated by vasoconstrictor COX products in young men, but evokes no consistent response in women in the low or high E2 phases of the menstrual cycle. © 2011 The Authors. Journal compilation © 2011 The Physiological Society.