The interaction of muscle fiber contraction with the activity of the sympathetic nerves is a major determinant of vascular resistance in striated muscle. In cheek pouch arterioles, propagated vasodilation (PVD) induced with acetylcholine iontophoresis has been defined as an increase in the diameter of resistance vessels at sites well removed from the initial stimulus.
A specific aim of this research proposal is to investigate PVD in response to muscle fiber contraction as a mechanism for coordinating the local control of blood flow among segments comprising the resistence network. It is hypothesized that: a) there is a threshold of striated muscle fiber activity required to induce PVD into arterioles that supply the active fibers, b) the magnitude of propagation will be related to be intensity of muscular contraction, and c) propagation functions to coordinate red cell flow (02 delivery) with local metabolic requirements of contracting fibers. Initial experiments will be performed on the hamster cremaster muscle. Muscle fibers are stimulated via microelectrodes positioned in the tissue; voltage and frequency are manipulated to control the activity of muscle fibers. Vasomotor responses, striated muscle fiber contraction, and arteriolar red cell flow are observed directly using intravital microscopy. Another aim of these studies is to investigate the interaction of PVD with sympathetic vasoconstriction (SVC). A longstanding question has focused on the """"""""escape"""""""" of resistance vessels in active tissue from SVC, traditionally explained by local metabolic production of vasodilators. It is hypothesized that a) PVD from active tissue may interact with SVC of arterioles, and thus be an integral component of """"""""functional sympatholysis"""""""" of microvessels, and b) feed arteries are the primary site of flow control during SVC. The interaction of PVD with SVC will be investigated in arterioles and the small feed arteries to determine if either control system dominates as a function of vessel size or location. SVC will be manipulated via the baroreflex using graded occlusions of either the carotid arteries or the inferior vena cava. These studies will illuminate the interaction of vasomotor stimuli arising from multiple locations (parenchymal cells, other vessel segments, sympathetic nerves), and define specific locations of blood flow control during muscular activity and SVC. Findings may offer novel methods for treatment of hypertension and ischemic disorders.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29HL041026-04
Application #
3472227
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1988-07-01
Project End
1992-06-30
Budget Start
1991-07-01
Budget End
1992-06-30
Support Year
4
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Organized Research Units
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Bertram, James P; Williams, Cicely A; Robinson, Rebecca et al. (2009) Intravenous hemostat: nanotechnology to halt bleeding. Sci Transl Med 1:11ra22
Kurjiaka, D T; Segal, S S (1996) Autoregulation during pressor response elevates wall shear rate in arterioles. J Appl Physiol 80:598-604
Ledvina, M A; Segal, S S (1995) Sarcomere length and capillary curvature of rat hindlimb muscles in vivo. J Appl Physiol 78:2047-51
Kurjiaka, D T; Segal, S S (1995) Interaction between conducted vasodilation and sympathetic nerve activation in arterioles of hamster striated muscle. Circ Res 76:885-91
Segal, S S; Kurjiaka, D T (1995) Coordination of blood flow control in the resistance vasculature of skeletal muscle. Med Sci Sports Exerc 27:1158-64
Kurjiaka, D T; Segal, S S (1995) Conducted vasodilation elevates flow in arteriole networks of hamster striated muscle. Am J Physiol 269:H1723-8
Segal, S S (1994) Cell-to-cell communication coordinates blood flow control. Hypertension 23:1113-20
Puri, R K; Segal, S S (1994) Microvascular responses to body tilt in cutaneous maximus muscle of conscious rats. J Appl Physiol 77:2426-33
Pierzga, J M; Segal, S S (1994) Spatial relationships between neuromuscular junctions and microvessels in hamster cremaster muscle. Microvasc Res 48:50-67
Williams, D A; Segal, S S (1993) Feed artery role in blood flow control to rat hindlimb skeletal muscles. J Physiol 463:631-46

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