• Unthank, Joseph, (PI)

Project: Research project


The objectives of this proposal are to determine exactly how small
collateral arteries and the microcirculation adapt to the chronic
impairment of arterial inflow and to evaluate potential mechanisms that may
mediate the acute and chronic vascular responses. For this purpose, I have
developed a chronic technique that makes it possible to repeatedly observe
the exact same vessels over a period of weeks to months. The entire
intestinal vasculature from the arteries in the mesentery to the arterioles
and capillaries of the submucosa and muscle layers can be studied. Pilot
studies have demonstrated that the severity of the arterial inflow problem
can be varied by the number of arteries ligated and that adult rats can
permanently tolerate up to a 50% reduction in tissue blood flow. I have
found that dilation of the small arteries and arterioles occurs immediately
after arterial occlusion and that within one week there is selective
enlargement of those collateral arteries and arterioles, which by their
anatomical location, must experience increased blood flow. Similar vessels
at the center of the collateral dependent region are not chronically
enlarged. Microvascular pressure measurements and calculations of
resistance indicate that microvascular pressures are restored to near
normal in about 1 week by decreased resistance through these chronically
enlarged collateral arteries and arterioles. I will evaluate the roles of
flow-dependent, EDRF-mediated vasodilation and oxygen-dependent metabolic
control in the vascular responses and test for the propagation of
vasodilation by cell-to-cell communication from one vascular segment to the
next. As the nature and course of compensation may evolve over time, the
vascular responses will be studied immediately after sudden arterial
occlusion and at early and late time points in the adaptive process. I
will also use different degrees of arterial inflow restriction to determine
how the severity of the initial insult influences the mechanisms involved
and the major site and format of the compensation. Additional insight into
the mechanisms involved will be obtained by selective placement of the
arterial ligatures so that, in some cases, the majority of collateral flow
occurs through small arteries located a considerable distance from the
dependent tissue and, in other cases, through arterioles immediately
adjacent to the dependent tissue. The effect of the chronic adaptation of
vessels on passive distensibility and vascular reactivity will also be
evaluated in collateral arteries and arterioles that are exposed to
chronically increased blood flow and in similar types of vessels in the
center of the collateral dependent tissue where blood flow and/or pressure
may be chronically depressed. These studies will be the first to evaluate
the same set of macro- and microscope vessels before occlusion and through
various stages of compensation following the onset of arterial occlusion.
The results will provide definitive information regarding the underlying
mechanisms which initiate either compensatory or pathological responses to
arterial restrictive disease and identify exactly what vessels are
Effective start/end date8/1/913/31/09


  • National Institutes of Health: $188,125.00
  • National Institutes of Health
  • National Institutes of Health: $100,381.00
  • National Institutes of Health: $167,788.00
  • National Institutes of Health
  • National Institutes of Health: $188,125.00
  • National Institutes of Health: $159,368.00
  • National Institutes of Health: $172,990.00
  • National Institutes of Health: $173,226.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $157,601.00
  • National Institutes of Health: $108,174.00


Blood Vessels
Nitric Oxide
Inbred SHR Rats
Vascular Diseases
Nitric Oxide Synthase
Gene Expression
Matched-Pair Analysis
Free Radical Scavengers
Gene Expression Regulation
Enzyme Inhibitors
Arterial Occlusive Diseases


  • Medicine(all)