The afferent arteriolar myogenic response contributes to the autoregulation of renal blood flow (RBF) and glomerular filtration rate (GFR), and plays an essential role in protecting the kidney against hypertensive injury. Systolic blood pressure (SBP) is most closely linked to renal injury, and a myogenic response coupled to this signal would facilitate renal protection, whereas mean blood pres...

Reactive oxygen species enhance or impair autoregulation. Because superoxide is a vasoconstrictor, we tested the hypothesis that stretch generates superoxide that mediates myogenic responses. Increasing perfusion pressure of mouse isolated perfused renal afferent arterioles from 40 to 80 mm Hg reduced their diameter by 13.3 1.8% (P 0.001) and increased reactive oxygen species (ethidium: dihydro...

Supraphysiological increases in serum triglycerides and cholesterol often occur during pregnancy, but their effects on vascular function are poorly understood. Intraperitoneal injection of the nontoxic surfactant poloxamer 407 (P-407) results in sustained elevation of triglycerides and cholesterol. We asked if P-407-induced hyperlipidemia during late pregnancy adversely affects mesenteric resis...

Previously, in an attempt to isolate stem cells that would be capable of regenerating injured skeletal muscle, we cultured cells derived from muscle, non-adherently, in serum-free media. As a result of the culture conditions used, these cells formed spheres, and thus were referred to as myospheres. It was found that myosphere-derived cells expressed Sca-1, a marker that is not typically associa...

Vertebrate myogenesis is regulated by signaling proteins secreted from surrounding tissues. One of the most important, Sonic hedgehog, has been proposed to regulate myogenic precursor cell survival, proliferation, and differentiation in a variety of vertebrates. In zebrafish, Hedgehog signaling is both necessary and sufficient for the development of embryonic slow muscle fibers-the earliest dif...

This work combines expertise in stem cell biology and bioengineering to define the system for geometric control of proliferation and differentiation of myogenic progenitor cells. We have created an artificial niche of myogenic progenitor cells, namely, modified extracellular matrix (ECM) substrates with spatially embedded growth or differentiation factors (GF, DF) that predictably direct muscle...

A number of genes, spanning the evolutionary scale from yeast to mammals, that are involved in spatial and temporal patterning during development contain zinc finger and homeodomain motifs. One such zinc finger/homeodomain protein is Drosophila Zfh-1, a member of the zfh family of Drosophila genes, which is expressed in muscle precursors and is critical for the proper development of muscle. Her...

Vertebrate muscle arises sequentially from embryonic, fetal, and adult myoblasts. Although functionally distinct, it is unclear whether these myoblast classes develop from common or different progenitors. Pax3 and Pax7 are expressed by somitic myogenic progenitors and are critical myogenic determinants. To test the developmental origin of embryonic and fetal myogenic cells in the limb, we genet...

The Brown Norway (BN) rat is normotensive and has an extended lifespan but is extremely sensitive to hypertension-induced renal injury. Relative impairment of autoregulation has been implicated in the progression of renal failure whereas absence of myogenic autoregulation is associated with early renal failure. Therefore, we tested the hypothesis that there is conditional failure of renal autor...

Characterization of myogenic subpopulations has traditionally been performed independently of their functional performance following transplantation. Using the preplate technique, which separates cells based on their variable adhesion characteristics, we investigated the use of cell surface proteins to potentially identify progenitors with enhanced regeneration capabilities. Based on previous s...