The objective of this application is to investigate the mechanisms by which 1,25 vitamin D3 modulates vascular smooth muscle myosin expression, calcium homeostasis and force generation. The investigator has previously demonstrated that 1, 25 vitamin D increases myosin regulatory light chain and myosin heavy chain protein expression in aorta but not in small resistance arteries. The investigator hypothesizes that 1, 25 vitamin D exerts regionally different actions on smooth muscle, that is a differentiating pro-myosin action in the aorta and a calciotropic action in the resistance arteries. This hypothesis will be tested by: 1. Determining the effect of 1, 25 vitamin D on myosin isoform expression, calcium mobilization, and contraction in aortic muscle from rats administered 1, 25 vitamin D for a three day period. 2. Determine if 1, 25 vitamin D selectively modulates expression of the smooth muscle specific isoforms of the myosin heavy chain. 3. Determine if 1, 25 vitamin D enhances agonist induced mobilization of intracellular calcium in the aorta. 4. Determine if vitamin D enhances force generation by a direct effect on myofilament calcium sensitivity unrelated to changes in calcium mobilization. 5. Using resistance arteries, the investigator will determine if 1, 25 vitamin D enhances calcium mobilization by increasing calcium influx. 6. Or determine if 1, 25 vitamin D increases release of intracellular calcium stores. 7. Determine if 1, 25 vitamin D increases calcium mobilization by decreasing calcium efflux or calcium removal from the cytosolic space. The investigator proposes that the resulting information from these studies will be clinically relevant because 1, 25 vitamin D is elevated in, and may contribute to, the vascular pathology in such conditions as gestational hypertension and post- menopausal women on estrogen supplements.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL054901-01
Application #
2233404
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1995-07-01
Project End
1999-05-31
Budget Start
1995-07-01
Budget End
1996-05-31
Support Year
1
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Texas Medical Br Galveston
Department
Otolaryngology
Type
Schools of Medicine
DUNS #
041367053
City
Galveston
State
TX
Country
United States
Zip Code
77555