Related Experiment Videos
Effects of activated polymorphonuclear leukocytes on vascular smooth muscle tone
J L Mehta1, D L Lawson, F A Nicolini
1Department of Medicine, University of Florida College of Medicine, Gainesville.
Abstract:
Unstimulated polymorphonuclear leukocytes (PMNLs) release nitric oxide or a like material that relaxes vascular tissues. To determine the effects of activated PMNLs on vascular tone, precontracted rat aortic rings were exposed to ionophore A23187-treated PMNLs. Whereas "unstimulated" PMNLs caused 29 +/- 4% relaxation, "stimulated" PMNLs caused initial contraction followed by 90 +/- 7% relaxation of aortic rings. Indomethacin or the 5-lipoxygenase blocker piriprost had no effect on PMNL-induced initial contraction or subsequent relaxation. However, initial contraction was abolished and the subsequent vasorelaxation attenuated (22 +/- 5%) by the superoxide radical scavenger superoxide dismutase (SOD), suggesting that release of superoxide radicals may have induced vascular contraction and caused endothelial damage that would permit unopposed vasorelaxant effect of PMNLs. To examine this hypothesis, aortic rings were exposed to superoxide radicals (generated by xanthine plus xanthine oxidase, X + XO) or manually deendothelialized. These rings revealed marked relaxation (78 +/- 6 and 85 +/- 6%, respectively) in response to unstimulated PMNLs. These observations suggest that stimulated PMNLs exert an initial vasoconstrictor effect and a subsequent vasorelaxant effect in response to release of superoxide radicals and nitric oxide, respectively. Arachidonate metabolites or 5-lipoxygenase products do not appear to be important in the actions of PMNLs on vascular smooth muscle.
Insights
Activated polymorphonuclear leukocytes (PMNLs) cause initial blood vessel contraction and subsequent relaxation. Superoxide radicals from PMNLs may cause contraction, while nitric oxide mediates relaxation.
Area of Science:
- Cardiovascular Physiology
- Inflammation Research
- Vascular Biology
Background:
- Polymorphonuclear leukocytes (PMNLs) are key immune cells involved in inflammation.
- Unstimulated PMNLs release nitric oxide (NO), a vasodilator.
- The effects of activated PMNLs on vascular tone are not fully understood.
Purpose of the Study:
- To investigate the impact of activated PMNLs on vascular tone.
- To elucidate the mechanisms underlying PMNL-induced vascular effects, including the roles of superoxide radicals and NO.
Main Methods:
- Rat aortic rings were precontracted and exposed to unstimulated or ionophore-stimulated PMNLs.
- Vascular responses were measured in the presence or absence of inhibitors and scavengers.
- Superoxide radicals were generated using xanthine/xanthine oxidase (X + XO) to mimic PMNL-derived radicals.
Main Results:
- Stimulated PMNLs induced initial contraction followed by significant vasodilation (90%).
- Superoxide dismutase (SOD) abolished the initial contraction and attenuated relaxation, implicating superoxide radicals.
- Deendothelialized or X + XO-treated rings showed enhanced relaxation to unstimulated PMNLs, supporting the role of endothelial damage and superoxide radicals.
Conclusions:
- Activated PMNLs exert a biphasic effect on vascular tone: initial vasoconstriction followed by vasodilation.
- Superoxide radical release by PMNLs contributes to initial vasoconstriction and potentially endothelial damage.
- Nitric oxide release by PMNLs mediates the subsequent vasorelaxant effect.