The purpose of the present proposal is to generate useful new information on the role of adrenergic in the development and maintenance of hypertension in the Spontaneously Hypetensive Rat (SHR). The present application is a logical extension of ongoing studies and will focus on two important aspects of our previous observations. First, to investigate the functional significance of the alterations in the relesse of norepinephrine (NE) from blood vessels and central brain regions of the SHR and secondly, to further characterize, explore and define the mechanisms contributing to the alterations in the release of NE from blood vessels and brain regions of the SHR. The overall unifying hypothesis to be examined is, """"""""There are defects at the level of noradrenergic nerve terminal in the periphery and the central nervous system resulting in alterations in transmitter release. Depending upon the neuroeffector junction in question, the increased release (blood vessels, posterior hypothalamus) and decreased release (anterior hypothalamus, A2 region of the NTS) of NE contributes to the development and/or maintenance of hypertension. Changes in the activity of prejunctional release modulatory receptors contribute to these alterations in transmitter release."""""""" The proposal has been divided into two parts. Part one deals with studies on peripheral noradrenergic transmission in the SHR and Part two deals with central noradrenergic transmission in the SHR.
The Specific Aims are: 1) to investigate the functional significance of the enhanced release of NE from isolated blood vessels and the importance of an alteration in prejunctional receptor activity in contributing to the enhanced release; 2) to further characterize and define the mechanism(s) for the enhancement of NE release by angiotensin in blood vessels of SHR; 3) to further characterize and define the mechanism for the attenuation of the yohimbine induced enhancement of NE release in blood vessels of the SHR; 4) to investigate the functional significance of alterations in the evoked release of NE from the brain using push-pull perfusion; 5) to determine if there are alterations in the activity of prejunctional release modulatory receptors in the CNS of SHR; and 6) to examine the role of vasopressin as possible modulator of NE release from brain regions of normal and hyoertensive rats. The proposal should generate useful new information on several aspects of the role of noradrenergic neurons in the development and maintenance of hypertension in the SHR and other hypertensive models.
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