Role of the renal nerves in hypertension
2014-11
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Role of the renal nerves in hypertension
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2014-11
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High blood pressure (hypertension; HTN) is the leading risk factor for death, yet the precise causes are unclear. The nervous system is known to play a role in some forms of HTN and research has pointed to the kidneys as a likely neural target in HTN. This possibility has been strengthened by recent clinical trials showing that ablation of the renal nerves (renal denervation; RDNX) has a significant antihypertensive effect in drug resistant patients. However, failure of the most recent sham-controlled trial has raised many questions regarding this treatment. Chief among them is whether the antihypertensive effect of RDNX is due to changes in kidney function secondary to ablation of sympathetic (efferent) renal nerves, or due to a reduction in non-renal sympathetic nerve activity secondary to ablation of sensory (afferent) renal nerves. In order to address this question, I first identified an animal model of HTN in which RDNX had an antihypertensive effect. Importantly, I showed that RDNX had roughly the same effect on blood pressure in hypertensive Dahl salt-sensitive (S) rats as has been reported in clinical trials. I then developed and validated a novel method for selective ablation of afferent renal nerves (renal-CAP treatment). Using this method, I showed that afferent renal nerves are not necessary to maintain cardiovascular or sodium/water homeostasis in normotensive rats subjected to dietary sodium loading. We also showed that renal-CAP treatment and complete RDNX caused the same attenuation of deoxycorticosterone-salt HTN, suggesting that the antihypertensive effect of RDNX in this model is due to ablation of afferent renal nerves. Lastly, we showed that RDNX has the same antihypertensive effect in Dahl S rats with mild HTN (after three weeks of high salt feeding) and in those with severe HTN (after nine weeks of high salt feeding). These results suggest that the antihypertensive effect of RDNX in the Dahl S rat is not dependent on duration of high salt feeding or pretreatment blood pressure and that the antihypertensive effect of RDNX in this model is not due to ablation of afferent renal nerves.
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University of Minnesota Ph.D. dissertation. November 2014. Major: Integrative Biology and Physiology. Advisor: John W. Osborn, PhD. 1 computer file (PDF); x, 125 pages.
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Foss, Jason David. (2014). Role of the renal nerves in hypertension. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/170122.
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