Norepinephrine (NE) is a vasoconstrictor neurotransmitter released from sympathetic nerves that innervate the smooth muscle cells in arteries and veins. Once released, NE diffuse across the junctional cleft, bind briefly to receptor to elicit smooth muscle contraction. The sympathetic nerves system regulates blood pressure and its function is altered in animal models and human essential hypertension. The altered function is associated with altered NE release. However, little is known about the characteristics of local NE release from periarterial and perivenous sympathetic nerves in normal and hypertensive animals. I seek a better understanding of the functional differences between sympathetic neurotransmission in mesenteric arteries (MA) and veins (MV), and how this process is altered in hypertension. Deoxycorticosterone-acetate (DOCA) salt rats were used as a model of salt-sensitive hypertension. Continuous amperometry with a microelectrode measures the local concentration of endogenous NE at the surface of a blood vessel as an oxidation current. Since NE release is a multi-step process, one way the mechanisms can be probed is by studying the temperature dependence of neurotransmitter release and clearance.

The results of this dissertation study revealed important findings regarding adrenergic neurotransmission in MA and MV from normotensive and DOCA-salt hypertensive rats. (1) NE release and clearance from rat periarterial and perivenous sympathetic nerves are regulated differently. This difference is based largely on the function of prejunctional α₂ adrenergic receptors (α₂ARs), NE transporter (NET), calcium channels, but may also include different distribution of vesicles that contain NE. NE release and clearance is regulated by α₂ARs and NET in MA but not in MV. (2) Adrenergic neurotransmission to MA is impaired in DOCA-salt hypertension. The increased NE overflows and temperature sensitivity in DOCA-salt MA is at least partially due to the impaired function of α₂AR and NET. These changes are not due to the alterations in calcium handling in the nerve terminal. (3) Oxidative stress alters sympathetic neurotransmission in DOCA-salt hypertensive rats by impairing pertussis toxin-sensitive G proteins which couple to α₂AR at the nerve terminal. Chronic antioxidant treatment lowers blood pressure and restores sympathetic nerve function at the neuroeffector junction in DOCA-salt hypertensive rats.

Together, these results reveal the different supply of sympathetic nerves to MA and MV may contribute to their different hemodynamic functions. Furthermore, they reveal the importance of sympathetic nerve endings as a therapeutic target and support a new mechanism for the beneficial effect of antioxidant treatment in salt-sensitive hypertension.