Anne M Dorrance1. 1. Department of Physiology, Medical College of Georgia, Augusta, GA 30912-3000, USA. adorrance@mcg.edu
Abstract
BACKGROUND: The chronic effects of interleukin 1-beta (IL-beta) on vascular reactivity include augmentation of contraction and relaxation. Few studies have assessed the acute effects of IL-1beta in vessels from hypertensive and normotensive rats. We hypothesized that IL-1beta would enhance constriction in aorta from stroke prone spontaneously hypertensive rats (SHRSP). METHODS: Endothelium denuded aortic rings from 12 week-old SHRSP and Wistar Kyoto (WKY) rats were mounted in a myograph and incubated with IL-1beta (20 ng/ml) for 1 h before construction of a phenylephrine dose response curve. Indomethacin (1 microM) and PP-2 (1 microM) were utilized to inhibit cyclooxygenase (COX) and Src-kinase respectively. RESULTS: In aorta from SHRSP, IL-1beta caused a significant increase in the force generated over the hour incubation; inhibition of COX or Src-kinase prevented this. The maximum phenylephrine-induced contraction was greater in aorta from SHRSP incubated with IL-1beta than control. COX or Src-kinase inhibition prevented this. IL-1beta had no effect on the vessels from WKY rats. CONCLUSIONS: These novel data suggest that IL-1beta has rapid effects on vascular smooth muscle from hypertensive rats to produce constriction and to enhance phenylephrine-induced constriction. The COX and Src-kinase pathways appear to be involved in this response.
BACKGROUND: The chronic effects of interleukin 1-beta (IL-beta) on vascular reactivity include augmentation of contraction and relaxation. Few studies have assessed the acute effects of IL-1beta in vessels from hypertensive and normotensive rats. We hypothesized that IL-1beta would enhance constriction in aorta from stroke prone spontaneously hypertensiverats (SHRSP). METHODS: Endothelium denuded aortic rings from 12 week-old SHRSP and Wistar Kyoto (WKY) rats were mounted in a myograph and incubated with IL-1beta (20 ng/ml) for 1 h before construction of a phenylephrine dose response curve. Indomethacin (1 microM) and PP-2 (1 microM) were utilized to inhibit cyclooxygenase (COX) and Src-kinase respectively. RESULTS: In aorta from SHRSP, IL-1beta caused a significant increase in the force generated over the hour incubation; inhibition of COX or Src-kinase prevented this. The maximum phenylephrine-induced contraction was greater in aorta from SHRSP incubated with IL-1beta than control. COX or Src-kinase inhibition prevented this. IL-1beta had no effect on the vessels from WKY rats. CONCLUSIONS: These novel data suggest that IL-1beta has rapid effects on vascular smooth muscle from hypertensiverats to produce constriction and to enhance phenylephrine-induced constriction. The COX and Src-kinase pathways appear to be involved in this response.
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