In both humans and most animal models (including the rat), normal pregnancy is characterized by increased blood volume and cardiac output, and decreased arterial blood pressure and total peripheral resistance. Renin and prostanoid synthesis are increased during pregnancy. Interestingly, pregnancy is associated with decreased pressor responsiveness to exogenously administered pressor agents: an effect which is reversed following blockade of prostaglandin synthesis. Obviously, major alterations in the neural-humoral control of the circulation would be necessary to accommodate the hemodynamic profile of normal pregnancy. However, few studies exist in which cardiovascular reflex mechanisms have been examined in pregnancy. The overall goal of the current proposal is to test the general hypothesis that during pregnancy adaptations occur in the neural control of the circulation at the level of the baroreceptors, the central nervous system and the peripheral vasculature which contribute to the hemodynamic profile characteristic of normal pregnancy. These adaptations could be related to the changes in blood volume, prostanoid production, and/or changes in the interaction between reflex systems. Experiments are planned in three groups of rats - nonpregnant, midterm-pregnant (progesterone dominant), and late-pregnant (estrogen dominant) - and comparisons will be made to determine the effects of pregnancy on: 1.) single unit afferent arterial baroreceptor discharge and the effects of blockade of prostanoid synthesis; 2.) arterial and cardiopulmonary baroreflex control of efferent regional sympathetic nerve activity and both the volume and chemical (prostanoids) sensitivity of cardiopulmonary receptors; 3.) parasympathetic and sympathetic components of reflex control of heart rate; 4.) baroreflex control of uterine vascular resistance and efferent sympathetic nerve activity to the uterus; and 5.) efferent responses to activation of cardiovascular related central nervous system sites. These experiments will yield new information on possible mechanisms for the cardiovascular adaptations of pregnancy. In addition, since failure of the normal adaptations is associated with serious pathological states such as pregnancy-induced hypertension, these studies will provide valuable clinically applicable information.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL036245-06
Application #
3351065
Study Section
Experimental Cardiovascular Sciences Study Section (ECS)
Project Start
1985-09-01
Project End
1995-01-01
Budget Start
1991-03-01
Budget End
1992-01-01
Support Year
6
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Ohio State University
Department
Type
Schools of Medicine
DUNS #
098987217
City
Columbus
State
OH
Country
United States
Zip Code
43210
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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