Pharmacological stimulation of the vagus nerve has been shown to suppress inflammation and reduce blood pressure in a murine model of systemic lupus erythematosus (SLE) that is characterized by hypertension, inflammation, renal injury and dysautonomia. The present study aims to directly stimulate vagal nerves at the level of the dorsal motor nucleus of the vagus (DMV) using designer receptors exclusively activated by designer drugs (DREADDs) to determine if there is similar protection and confirm mechanism. Female NZBWF1/J (SLE) mice and NZW/LacJ mice (controls, labeled as NZW throughout) received bilateral microinjections of pAAV-hSyn-hM3D(Gq)-mCherry or control virus into the DMV at 31 weeks of age.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
June 2020
T-helper (T)17s, IL-17, and cytolytic natural killer cells (cNKs) are increased in preeclampsia and contribute to the hypertension, inflammation, and fetal growth restriction that occurs in response to placental ischemia in the reduced uterine perfusion pressure (RUPP) rat model of preeclampsia. As IL-17 stimulates NK cytotoxicity in vitro, we tested the hypothesis that IL-17 inhibition in RUPP rats would decrease cNK activation as a mechanism to improve maternal and fetal outcomes. On gestation (GD) , rats undergoing RUPP received a miniosmotic pump infusing IL-17RC (100 pg/day), a soluble IL-17 receptor (RUPP + IL-17RC).
View Article and Find Full Text PDFThe present study examined whether development of renal injury in the nondiabetic obese Dahl salt-sensitive leptin receptor mutant (SSmutant) strain is associated with elevations in glomerular filtration rate and renal lipid accumulation. Baseline mean arterial pressure at 6 wk of age was similar between Dahl salt-sensitive wild-type (SS) and SSmutant rats. However, by 18 wk of age, the SSmutant strain developed hypertension, while the elevation in mean arterial pressure was not as severe in SS rats (192 ± 4 and 149 ± 6 mmHg, respectively).
View Article and Find Full Text PDFPrevious studies by our lab have established that placental-ischemia stimulated T-helper 17 cells (T 17s) cause increased cytolytic natural killer (cNK) cell proliferation and activation during pregnancy; however, the exact mechanism is unknown. The objective of this study was to investigate the role of interlukin 17 (IL-17) in inducing cNK cell activation in pregnancy. We infused 150 pg/day of recombinant IL-17 into a subset of normal pregnant (NP) Sprague Dawley rats from gestation day (GD) 12-19 (NP+IL-17).
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