Wall Remodeling During Luminal Expansion of Mesenteric Arterial Collaterals in the Rat

Abstract

Wall remodeling associated with rapid luminal enlargement of collateral mesenteric arteries in rats was investigated 1 and 4 weeks after creation of a collateral pathway by ligating three to four sequential arteries. Paired observations were made of inner diameters of collateral and normal arteries in the same animals. Arterial blood flow was measured at the final observation. Sections of arteries were processed for morphological measurements. After 4 weeks, inner arterial diameter was increased more at the beginning (63±6%) than the end (25±9%) of the collateral pathway. At 1 and 4 weeks, respectively, cross-sectional areas of collateral relative to normal arteries were increased by 46±5% and 59±13% (lumen), 55±8% and 65±14% (media), and 89±18% and 60±31% (intima). The wall expansion during luminal enlargement resulted in a normal medial thickness:luminal radius relationship. At 1 week postligation, wall shear rate remained elevated and endothelial but not smooth muscle hyperplasia had occurred (intimal nuclei: 40±1.7 collateral versus 24±3.0 normal; medial nuclei: 42±6.8 collateral versus 37±2.1 normal). At 4 weeks, wall shear rate in collaterals was similar to normal arteries, and smooth muscle hyperplasia had taken place (medial nuclei: 84±9.4 collateral versus 44±4.7 normal). The data demonstrate that wall expansion associated with rapid luminal enlargement of these collaterals involves hyperplasia of both endothelial and smooth muscle cells; however, smooth muscle proliferation does not occur until after wall shear rate is reduced. The specific cellular adaptations that occur during collateral development may depend on the level of wall shear and shear-dependent modulation of endothelial growth factors.