The applicant's immediate goals are to identify fundamental differences in the neural control of the sympathetic nervous system between male and female rats as it pertains to the development of hypertension. The applicant's long-term goals are to investigate the role of sex hormones on cardiovascular and renal regulation in pregnancy with a special interest in how cardiovascular and renal regulatory mechanisms are altered in the development of preeclampsia. This award will enhance the applicant's development as an independent investigator by allowing the applicant 1) to learn various techniques critical in evaluating the neural control of the sympathetic nervous system and combine these techniques with those in which the applicant is already proficient to attain her research goals; 2) to work in an environment which allows interaction with scientists from several departments knowledgeable in the area of neural mechanisms of hypertension; 3) to obtain preliminary data which is critical for a strong NIH - FIRST Award application. In human essential hypertension males develop higher levels of blood pressure than females. It has been postulated that estrogen protects against the development of hypertension. The first goal of this project is to test the hypothesis that estrogen alters the regulation of the sympathetic nervous system such that female rats more efficiently decrease sympathetic nerve activity in response to acute activation of arterial and cardiopulmonary baroreceptors resulting in an attenuated hypertension in Dahl salt-sensitive (S) females. The second goal is to propose and define a centrally mediated neural mechanism by which the sympathetic nervous system can be inhibited by estrogen. The hypothesis to be tested is that a noradrenergic-gamma-aminobutyric acid (GABA)ergic pathway exists in the anterior hypothalamus which is involved in sympathoinhibition which can be activated by estrogen. Central microinjection studies and microdialysis studies to measure the release of norepinephrine and GABA in the anterior hypothalamic area are proposed to establish the existence of a noradrenergic-GABAergic sympathoinhibitory relationship. Additional experiments using microinjections of noradrenergic agonists and antagonists as well as GABAergic agonists and antagonists will determine if estrogen stimulates the noradrenergic and/or the GABAergic component of the sympathoinhibitory pathway during basal conditions and during baroreflex activation.
|Hinojosa-Laborde, C; Lange, D L; Haywood, J R (2000) Role of female sex hormones in the development and reversal of dahl hypertension. Hypertension 35:484-9|
|Lange, D L; Haywood, J R; Hinojosa-Laborde, C (2000) Endothelin enhances and inhibits adrenal catecholamine release in deoxycorticosterone acetate-salt hypertensive rats. Hypertension 35:385-90|
|Hinojosa-Laborde, C; Lange, D L (1999) Endothelin regulation of adrenal function. Clin Exp Pharmacol Physiol 26:995-9|
|Hinojosa-Laborde, C; Chapa, I; Lange, D et al. (1999) Gender differences in sympathetic nervous system regulation. Clin Exp Pharmacol Physiol 26:122-6|
|VanNess, J M; Hinojosa-Laborde, C; Craig, T et al. (1999) Effect of sinoaortic deafferentation on renal wrap hypertension. Hypertension 33:476-81|
|Lange, D L; Haywood, J R; Hinojosa-Laborde, C (1998) Role of the adrenal medullae in male and female DOCA-salt hypertensive rats. Hypertension 31:403-8|
|Haywood, J R; Hinojosa-Laborde, C (1997) Sexual dimorphism of sodium-sensitive renal-wrap hypertension. Hypertension 30:667-71|