When blood flow in a large artery is increased, the vessel dilates. This flow dependent dilation is not mediated by myogenic mechanisms, an ascending message from the microcirculation, Alpha or Beta receptors, or prostaglandins. We have recently demonstrated that the dilation is endothelial cell dependent, involves both a non-prostaglandin metabolite of arachidonic acid and cyclic GMP, and is very sensitive to decreases in ionized plasma calcium. This proposal is designed to examine the physiological significance of flow dependent dilation and the pathophysiologic importance of its absence. Specifically, experiments are designed to determine the effect of shear stress on the dilation response and to define the precise role for calcium in endothelial dependent relaxation in vivo. We will determine the contribution of flow dilation in exercise hyperemia during 3 Hz. exercise and in chronically prepared dogs trained to run on a treadmill. We will evaluate the effects of hypercholesterolemia, atherosclerosis, and diabetes on endothelial dependent dilations in vivo and correlate these with in vitro vasoactivity. We will assess the role of intra-endothelial cell communication in the """"""""ascending dilation"""""""" seen with the distal injection of acetylcholine. Finally, we will investigate the effect of canine heartworm (D. immitis) infection on femoral artery vasoreactivity in vivo and in vitro. Our preliminary data shows that adult heartworms, in the pulmonary circulation, adversely influences femoral artery reactivity.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001842-04
Application #
3082233
Study Section
Research Manpower Review Committee (MR)
Project Start
1987-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Michigan State University
Department
Type
Schools of Medicine
DUNS #
193247145
City
East Lansing
State
MI
Country
United States
Zip Code
48824
Tithof, P K; Schwartz, A J; Mupanomunda, M et al. (1994) Dirofilaria immitis: depression of endothelium-dependent relaxation of canine femoral artery seen in vivo does not persist in vitro. Exp Parasitol 79:159-65
Lamb, V L; Schwartz, A J; Rohn, W R et al. (1994) Cyclooxygenase inhibitors depress norepinephrine constriction of rat abdominal, but not thoracic, aorta. Eur J Pharmacol 256:221-6
Collins, J M; Williams, J F; Kaiser, L (1994) Dirofilaria immitis: heartworm products contract rat trachea in vitro. Exp Parasitol 78:76-84
Lamb, V L; Williams, J F; Kaiser, L (1993) Effect of serum from dogs infected with Dirofilaria immitis on endothelium-dependent relaxation of rat aorta in vitro. Am J Vet Res 54:2056-9
Kaiser, L; Lamb, V L; Tithof, P K et al. (1992) Dirofilaria immitis: do filarial cyclooxygenase products depress endothelium-dependent relaxation in the in vitro rat aorta? Exp Parasitol 75:159-67
Kaiser, L; Ptu, S (1992) Effects of increasing age on vascular responses of the in vivo femoral artery of adult beagles. Gerontology 38:121-6
Kaiser, L; Tithof, P K; Lamb, V L et al. (1991) Depression of endothelium-dependent relaxation in aorta from rats with Brugia pahangi lymphatic filariasis. Circ Res 68:1703-12
Kaiser, L; Tithof, P K; Williams, J F (1990) Depression of endothelium-dependent relaxation by filarial parasite products. Am J Physiol 259:H648-52
Kaiser, L; Spickard, R C; Sparks Jr, H V et al. (1989) Dirofilaria immitis: alteration of endothelium-dependent relaxation in the in vivo canine femoral artery. Exp Parasitol 69:9-15
Kaiser, L; Spickard, R C; Olivier, N B (1989) Heart failure depresses endothelium-dependent responses in canine femoral artery. Am J Physiol 256:H962-7

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