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Transforming growth factor-beta 1 (TGF-beta 1) is strongly expressed during embryogenesis and in sites undergoing intense development and morphogenesis. Two receptor serine/threonine kinases (types I and II) have been identified as signal-transducing TGF-beta receptors. This study was undertaken to further explore the role of the distinct TGF-beta receptors during kidney development. The species-specific sequence information for the two T beta R-I, namely, activin receptor-like kinase-5 (ALK-5) and Tsk7L, in the rat was sought. Two full-length T beta R-I cDNAs were cloned from a neonatal rat kidney and lung libraries, and sequencing revealed that they were the rat homologs of human ALK-5 and murine Tsk7L. Both types I and II TGF-beta receptors are expressed in the kidney as determined by Northern blot analysis. T beta R-II mRNA abundance was significantly greater in the neonatal rat kidney compared with the adult rat kidney. Similarly, ALK-5 mRNA was more highly expressed in the fetal and neonatal rat kidney than the adult rat kidney. In contrast, there was no significant difference in Tsk7L mRNA abundance among the fetal, neonatal, and adult rat kidney. Thus, based on these findings, both T beta R-II and ALK-5 are developmentally regulated in the kidney. Increased expression of T beta R-II and ALK-5 proteins in the developing kidney was confirmed by immunohistochemistry. Interestingly, the two TGF-beta receptors did not entirely colocalize, raising the intriguing possibility that other TGF-beta signaling receptors may be involved.

Morphometric information on the terminal arteriolar networks (n = 10) in cat sartorius muscle [Koller et al., Am. J. Physiol. 253 (Heart Circ. Physiol. 22): H154-H164, 1987] is utilized in the calculations of distribution of vascular hindrance throughout the networks. These networks have tree-type geometry, i.e., they do not contain closed loops. The results are discussed in terms of simulated flow distribution. The flow calculations are based on the exact geometry of the arteriolar networks (the control and dilated diameter and the length of each vascular segment) and on assumed values of postarteriolar resistances. Three cases of postarteriolar resistances are considered: zero, constant, and randomly distributed. With zero postarteriolar resistances, the distribution of flow in the terminal arteriolar segments would be highly heterogenous. The simulated flow in each terminal segment is determined primarily by the number of bifurcations on the pathway leading to the terminal segment, with a slight compensation for the length of the pathways. The coefficient of variation of flow in the control state, CV(Qc), would be close to the value in the dilated state, CV(Qd). When each of the terminal segments is connected to a constant postarteriolar resistance, the CV's in both states decrease. The coefficient of variation in the dilated state becomes significantly smaller than in the control state. When postarteriolar resistances are randomly distributed, both CV's increase, and their values become closer to each other. These results suggest that postarteriolar resistances may play a very important role in distribution of flow in the microvascular network. This study formulates a framework for the quantification of the effect of arteriolar dilation on flow redistribution in the network.