Aging and hypertension cause similar changes in the wall structure of intracerebral arterioles. However, little data directly relate these structural changes with altered contractile function of the vessel wall or with dynamic changes in cerebrovascular resistance. Our overall objective is to study the biomechanical properties and responsiveness of isolated intracerebral arterioles from three strains of rat (F344, WKY and SHR) at 3, 12 and 16 to 24 months of age. These physiological characteristics will then be correlated with arteriolar wall structure from vessels fixed in vitro after physiologic study and in situ after pressure perfusion fixation.
The specific aims are: 1) to determine the effect of aging and hypertension on active stress development and wall compliance in cerebral arterioles; 2) to determine the relative effects of aging and hypertension on cerebrovascular reactivity and on sensitivity to putative metabolic and neurogenic modulators of cerebrovascular resistance; 3) to correlate biomechanical characteristics of intracerebral arterioles from aged and hypertensive rats and humans with morphological indicators of vessel wall mass: partial volumes of actin and connective tissue, cell volume and cell number. Structure-function relationships established for these well characterized animal models will be extended to human intracerebral arterioles obtained at operation. These studies should enhance our understanding of how the microcirculation is affected by aging and hypertension, and how these changes relate to the major pathophysiologic sequelae of hypertension in the brains of aged individuals, thrombotic infarction and intracerebral hemorrhage.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
7R01HL037983-04
Application #
3353996
Study Section
Special Emphasis Panel (SRC (01))
Project Start
1989-12-01
Project End
1991-11-30
Budget Start
1989-12-01
Budget End
1990-11-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Washington University
Department
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Dietrich, H H; Kimura, M; Dacey Jr, R G (1994) N omega-nitro-L-arginine constricts cerebral arterioles without increasing intracellular calcium levels. Am J Physiol 266:H1681-6
Dietrich, H H; Dacey Jr, R G (1994) Effects of extravascular acidification and extravascular alkalinization on constriction and depolarization in rat cerebral arterioles in vitro. J Neurosurg 81:437-42
Kimura, M; Dietrich, H H; Huxley, V H et al. (1993) Measurement of hydraulic conductivity in isolated arterioles of rat brain cortex. Am J Physiol 264:H1788-97
Ogura, K; Takayasu, M; Dacey Jr, R G (1991) Differential effects of intra- and extraluminal endothelin on cerebral arterioles. Am J Physiol 261:H531-7
Ogura, K; Takayasu, M; Dacey Jr, R G (1991) Effects of hypothermia and hyperthermia on the reactivity of rat intracerebral arterioles in vitro. J Neurosurg 75:433-9
Ogura, K; Takayasu, M; Dacey Jr, R G (1991) Differential effects of pentobarbital on intracerebral arterioles and venules of rats in vitro. Neurosurgery 28:537-41
Takayasu, M; Dacey Jr, R G (1989) Spontaneous tone of cerebral parenchymal arterioles: a role in cerebral hyperemic phenomena. J Neurosurg 71:711-7
Takayasu, N; Dacey Jr, R G (1989) Effects of mannitol on intracerebral arteriolar diameter in vitro: extraluminal and intraluminal application. Neurosurgery 25:747-51;discussion 751-2
Dacey Jr, R G; Bassett, J E; Takayasu, M (1988) Vasomotor responses of rat intracerebral arterioles to vasoactive intestinal peptide, substance P, neuropeptide Y, and bradykinin. J Cereb Blood Flow Metab 8:254-61