Abstract
Hypertension (HTN) is a multifactorial disease affecting one-third of adults in western society. It is well established that renal artery stenosis results in secondary renovascular HTN. Experimentally, renovascular HTN is induced in rats by creating stenosis of the left renal artery, thereby decreasing perfusion pressure while the contralateral kidney remains intact (2K1C-HTN). This leads to increases in renin-angiotensin system activity, mean arterial pressure (MAP), sympathetic nerve activity, thirst, and renal inflammation. The organum vasculosum of the lamina terminalis (OVLT) has been implicated in the regulation of MAP, sympathetic activity, and thirst. In the present study, we investigated the role of the OVLT in the rat model of 2K1C-HTN.Male Sprague-Dawley rats (n=6-8/group) were randomly selected to receive either electrolytic lesion of the OVLT (OVLTx) or sham operation. One week after lesion or sham-lesion, rats were instrumented with telemeters to continuously measure MAP. The following week the rats received a silver clip around the left renal artery to generate 2K1C-HTN or sham-clip surgery. MAP was measured for 6 weeks after clip or sham-clip and, once a week, rats were housed in metabolic cages for 24 hours to measure water intake and urine volume. Urine was analyzed for inflammatory cytokines and copeptin, a surrogate marker of vasopressin. Neurogenic pressor activity (NPA) was assessed on the last day of the experiments by measuring the peak MAP response to ganglionic blockade. Upon completion of the study, rats were euthanized, and kidneys removed for measurement of inflammatory cytokine content.At the end of the protocol, MAP was significantly (p<0.001) higher in sham OVLT-2K1C (162±6 mmHg) compared to sham OVLT-sham-clip (105±0.7 mmHg) rats. MAP was lower in OVLTx-2K1C (135±8 mmHg) compared to sham OVLT-2K1C rats. NPA was increased in sham OVLT-2K1C rats (-51 ± 3 mmHg) compared to sham OVLT-sham-clip (-26 ± 4 mmHg) and it was reduced in OVLTx-2K1C rats (-31 ± 4 mmHg) (p<0.05). In addition, water intake was significantly (p<0.001) lower in OVLTx-2K1C (52±9 ml/day) compared to sham OVLT-2K1C (74±9 ml/day) rats. Urine output was reduced in OVLTx-2K1C (25±2 ml/day) compared to sham OVLT-2K1C (44±7 ml/day) rats. From the second week of study, urinary copeptin levels were lower in OVLTx-2K1C compared to sham OVLT-2K1C throughout development of 2K1C-HTN. Levels of IL1β and TNFα were significantly lower in the kidneys and urine of OVLTx rats than sham OVLT rats: IL1β (renal: 21±2 vs.44±8; urinary: 149±113 vs.479±201) and TNFα (renal: 0.12±0.02 vs. 0.24±0.01; urinary: 4±2 vs. 19±7), respectively.Taken together these results suggest that the OVLT is required for the development of hypertension, polydipsia, AVP release and renal inflammation in 2K1C-HTN. JO is funded by NIH R01 HL116476. LE is funded by NIH R01 HL152166. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
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