Absorption of food molecules is the major requirement for life. In the intestinal villus, absorption is a complex cellular process supported by the microvasculature and lymphatic system. During absorption of glucose, amino acids, and lipids, the villus interstitium develops a gradient of osmolarity from the base to the apex in the range of 450 to over 600 mOsm. Even at rest, the villus apex is more hypertonic and has a lower oxygen tension than at the base. Villus hyperosmolarity has implications for regulation of intestinal blood flow during food absorption. Data I obtained indicate the environment around major resistance arterioles of the submucosa becomes hypertonic due to the passage of hypertonic lymph and venular blood from the mucosal tissue. Perfusion of the lymph vessels with hypertonic media causes sustained dilation of the submucosal arterioles and about half of the dilation is linked to a sodium induced release of endothelial derived relaxing factor. The large arterioles and small arteries of the small intestine are proposed to be the dominant vessels responsible for decreased resistance and increased blood flow during absorptive hyperemia. The mechanism of dilation for large arterioles is primarily related to sodium induced hyperosmolarity caused by return of hypertonic blood and lymph from the mucosa and this can be tested by duplication of same sodium hyperosmolarity as occurs beside each arteriole during glucose or oleic acid absorption. The processes of counter-current exchange of oxygen and simultaneous counter-current exchange and multiplication of absorbed materials have been proposed to explain the origin of the intestinal hyperosmolarity and the higher oxygen tension in the villus base than apex. However, a much simpler explanation is possible. The fundamental cellular mechanism which establishes the gradient of osmolarity and oxygen tension from the villus apex to base may be greater sodium ion absorption at rest and cellular co-transport of amino acids and glucose with sodium molecules in the apical than basal portions of the villus. The hypertonic interstitial fluid produced in the villus apex is moved by the flow of lymph from the villus apex to base in the lacteal system. The osmolarity at the villus base and submucosal layer is raised by equilibration with the more hypertonic lymph from the villus apex. The flow of lymph keeps the osmotic gradient from villus apex to base smaller than would expected due to the proposed major differences in absorptive rates along the villus shaft both at rest and during nutrient absorption. The greater absorption rate of sodium at rest and sodium with carbohydrates or amino acids in the apical than basal portions of the villus is potentially responsible for the reduction in oxygen tension from villus base to apex, rather than counter-current oxygen exchange in the villus. However, counter-current exchange of oxygen between arterioles and venules in the submucosa is likely because pilot studies indicate the percent saturation of hemoglobin is 15-25% in small venules compared to 40-60% in large venules. The efficiency of counter-current exchange of oxygen should be diminished as blood flow increases, which would reduce oxygen loss from the arterioles preceding the villus tissue. The overall hypothesis is that hyperosmolarity generated in the mucosa during nutrient absorption is a signal for dilation of the resistance vessels and oxygen delivery to the mucosa is improved by increased oxygen content of arteriolar blood due to decreased counter-current exchange of oxygen.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL020605-17
Application #
2215372
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1977-04-01
Project End
1998-12-31
Budget Start
1994-01-01
Budget End
1994-12-31
Support Year
17
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Indiana University-Purdue University at Indianapolis
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
005436803
City
Indianapolis
State
IN
Country
United States
Zip Code
46202
Bohlen, Harold Glenn (2015) Nitric oxide and the cardiovascular system. Compr Physiol 5:808-23
Bohlen, H Glenn (2013) Is the real in vivo nitric oxide concentration pico or nano molar? Influence of electrode size on unstirred layers and NO consumption. Microcirculation 20:30-41
Bohlen, H Glenn (2011) Rapid and slow nitric oxide responses during conducted vasodilation in the in vivo intestine and brain cortex microvasculatures. Microcirculation 18:623-34
Zhou, Xiaosun; Bohlen, H Glenn; Unthank, Joseph L et al. (2009) Abnormal nitric oxide production in aged rat mesenteric arteries is mediated by NAD(P)H oxidase-derived peroxide. Am J Physiol Heart Circ Physiol 297:H2227-33
Bohlen, H G; Zhou, X; Unthank, J L et al. (2009) Transfer of nitric oxide by blood from upstream to downstream resistance vessels causes microvascular dilation. Am J Physiol Heart Circ Physiol 297:H1337-46
Payne, Gregory A; Bohlen, H Glenn; Dincer, U Deniz et al. (2009) Periadventitial adipose tissue impairs coronary endothelial function via PKC-beta-dependent phosphorylation of nitric oxide synthase. Am J Physiol Heart Circ Physiol 297:H460-5
Pezzuto, Laura; Bohlen, H Glenn (2008) Extracellular arginine rapidly dilates in vivo intestinal arteries and arterioles through a nitric oxide mechanism. Microcirculation 15:123-35
Bohlen, H Glenn (2008) Metalloproteinases damage the insulin receptor to cause insulin resistance in spontaneously hypertensive rats. Hypertension 52:215-7
Zhou, Xiaosun; Bohlen, H Glenn; Miller, Steven J et al. (2008) NAD(P)H oxidase-derived peroxide mediates elevated basal and impaired flow-induced NO production in SHR mesenteric arteries in vivo. Am J Physiol Heart Circ Physiol 295:H1008-H1016
Bauser-Heaton, Holly D; Song, Jin; Bohlen, H Glenn (2008) Cerebral microvascular nNOS responds to lowered oxygen tension through a bumetanide-sensitive cotransporter and sodium-calcium exchanger. Am J Physiol Heart Circ Physiol 294:H2166-73

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