| Numerous studies have reported that norepinephrine (NE) levels in the plasma of hypertensive humans and animals are elevated due to increased sympathetic nerve activity. Little is known, however, about how the kinetics and mechanism of NE release from perivascular sympathetic nerves as well as the postjunctional response is altered in hypertension. The first goal of my research was to design and implement continuous amperometric monitoring method and video imaging to record real time NE overflow from sympathetic nerves innervating arteries and veins and the evoked contractile response of isolated mesenteric veins (MV) and arteries (MA). The research included fabrication and characterization of a new microelectrode material, boron-doped diamond. The second goal was to use these two techniques to probe the functional differences in sympathetic neural control of MA and MV, and how the control mechanisms are altered in salt-sensitive hypertension. The deoxycorticosterone acetate (DOCA)-salt animal model for salt sensitive hypertension was used.; The results showed that the diamond microelectrode provided superior response performance as compared to a carbon fiber in terms of response precision and stability in tissue. Diamond exhibited resistance to fouling, least in part, because of the non-polar, low-oxygen, sp3-bonded carbon surface on which weak adsorption of polar biomolecules and other contaminants occurs. The results also confirmed that first there are fundamental differences in sympathetic neural control of MA and MV. These differences are: (i) the density and arrangement of sympathetic nerves in MA and MV, with MA having a higher density than MV, (ii) electrical stimulation-evoked NE overflow was exceeded in MV than MA in sham rats because NE release and clearance in MA were more strongly regulated by prejunctional alpha2-adrenergic autoreceptor and norepinephrine transporter (NET), respectively compared with MV, (iii) frequency-response vasoconstriction in MV was more sensitive than MA, (iv) in small MA, ATP was the dominant neurotransmitter, whereas in small MV, NE was the transmitter mediating constriction. The neural control mechanism of MA and MV were altered in the DOCA-salt animal model for hypertension as compared to sham control. This was evidenced by these findings: (i) NE overflow increased in DOCA-salt rat MA compared to sham MA due to, at least in part, an altered function of the prejunctional alpha2-adrenergic autoreceptor. The elevated NE overflow caused an increase in NE uptake in DOCA-salt MA. (ii) ATP mediated the neurogenic constriction of MA from sham rats while NE mediated most neurogenic constriction in DOCA-salt MA. This may be due to an increased adrenergic component of neurogenic constriction in DOCA-salt MA. (iii) the maximum contractile response was decreased in DOCA-salt MV, though NE overflow was not different between sham and DOCA-salt MV. It may be due to the desensitization of alpha1-adrenergic receptors or/and due to the altered vasculature in DOCA-salt MV.; Taken together, the differences in neuroeffector transmission may contribute to the different hemodynamic function of arteries and veins. Furthermore, the altered neuroeffector transmission in hypertension may contribute to the elevation in blood pressure. |
