The arterial baroreceptors play a major role in the regulation of arterial blood pressure in acute cardiovascular stresses such as hemorrhage and in pathophysiologic states such as hypertension. Activation of the arterial baroreceptors during a rise in arterial pressure provokes a reflex inhibition of sympathetic activity and a buffering of the rise in arterial pressure. The level of arterial pressure at which these receptors will fire and their sensitivity to changes in pressure is therefore an important determinant of the neural regulation of arterial pressure. For example, in hypertensive states, these baroreceptors are """"""""reset"""""""" so that they fire at a higher pressure and their sensitivity is reduced, contributing to the sustained elevation of arterial pressure (chronic resetting). This phenomenon of resetting also occurs in normotensive animals following temporary elevations of arterial pressure over a period of 10-15 minutes (acute resetting). The purpose of the proposed studies is to examine: 1) the relative degree of acute resetting of baroreceptors with myelinated and unmyelinated afferent fibers; 2) the possible contribution of circulating peptides (angiotensin II and vasopressin) to acute resetting of aterial baroreflexes; 3) regional differences in sympathetic outflow in response to brief changes (10-15 min.) in arterial pressure; 4) the central nervous system response to brief changes in afferent baroreceptor input, and 5) differences between normotensive and hypertensive animals in any of the above responses. Single unit baroreceptor discharge will be recorded in both myelinated and unmyelinated afferent fibers and responses to acute changes in pulsatile pressure will be examined. Efferent sympathetic nerve activity will be recorded and reflex control of regional sympathetic outflow (lumbar & renal) will be assessed following brief alterations in the prevailing pressure. In order to assess the contribution of circulating peptides to these responses, the experiments will be repeated in the presence of blockers of vasopressin and the renin-angiotensin system. Central mechanisms will be examined by manipulating the central afferent input (electrical stimulation of afferent nerves) and observing the effects on reflex control of efferent sympathetic nerve activity. Comparison of responses in normotensive and hypertensive animals should yield insight into both physiologic and pathophysiologic mechanisms involved in the reflex neural- humoral control of the circulation.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL036245-05
Application #
3351067
Study Section
Cardiovascular and Renal Study Section (CVB)
Project Start
1985-09-01
Project End
1990-12-31
Budget Start
1990-01-01
Budget End
1990-12-31
Support Year
5
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Kentucky
Department
Type
Schools of Medicine
DUNS #
832127323
City
Lexington
State
KY
Country
United States
Zip Code
40506
Heesch, Cheryl M (2011) Neurosteroid modulation of arterial baroreflex function in the rostral ventrolateral medulla. Auton Neurosci 161:28-33
Brooks, Virginia L; Dampney, Roger A L; Heesch, Cheryl M (2010) Pregnancy and the endocrine regulation of the baroreceptor reflex. Am J Physiol Regul Integr Comp Physiol 299:R439-51
Heesch, Cheryl M; Zheng, Hong; Foley, C Michael et al. (2009) Nitric oxide synthase activity and expression are decreased in the paraventricular nucleus of pregnant rats. Brain Res 1251:140-50
Kvochina, Lyudmyla; Hasser, Eileen M; Heesch, Cheryl M (2009) Pregnancy decreases GABAergic inhibition of the hypothalamic paraventricular nucleus. Physiol Behav 97:171-9
Kvochina, Lyudmyla; Hasser, Eileen M; Heesch, Cheryl M (2007) Pregnancy increases baroreflex-independent GABAergic inhibition of the RVLM in rats. Am J Physiol Regul Integr Comp Physiol 293:R2295-305
Heesch, Cheryl M; Laiprasert, Jennifer D; Kvochina, Lyudmyla (2006) RVLM glycine receptors mediate GABAA and GABAB)independent sympathoinhibition from CVLM in rats. Brain Res 1125:46-59
Foley, C Michael; Stanton, Jeffery J; Price, Elmer M et al. (2003) GABA(A) alpha1 and alpha2 receptor subunit expression in rostral ventrolateral medulla in nonpregnant and pregnant rats. Brain Res 975:196-206
Laiprasert, J D; Hamlin, R L; Heesch, C M (2001) Afferent baroreceptor discharge in pregnant rats. Am J Physiol Heart Circ Physiol 281:H2456-62
Masilamani, S; Heesch, C M (1997) Effects of pregnancy and progesterone metabolites on arterial baroreflex in conscious rats. Am J Physiol 272:R924-34
Heesch, C M; Crandall, M E; Turbek, J A (1996) Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow. Am J Physiol 270:R728-37

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