Hypertension affects nearly 1 billion people worldwide and is a leading risk factor for many cardiovascular diseases that in many cases, presents asymptomatically. Neruopilin-1 (NRP1) is a transmembrane receptor found in vascular smooth muscle (VaSMC) that binds to Class 3 Semaphorin (SEMA) ligand SEMA3A. In vitro RhoA inhibition has been observed to be mediated by NRP1 and SEMA3A interactions but its role in VaSMC have yet to be studied. We hypothesize that the ablation of NRP1 from VaSMC will cause the loss of pro-relaxant stimuli and therefore increase vascular tone and blood pressure in vivo. Using transgenic mice models, inducible VaSMC specific deletion of floxed Nrp1 was achieved using an incorporated cre recombinase enzyme knocked into an SM22α allele. Systolic blood pressure (SBP) was measured using a tail cuff method of litter- and sex-matched mice of control (SM22α+/+; Nrp1f/f) and experimental mice (SM22αcre/+; Nrp1f/f). SBP increased significantly in 11-week-old young male mice after 1 week of 4-hydroxy tamoxifen (4-OHT) treatment compared to control mice and baseline levels measured the previous week (146.6 ± 13.4 versus 105.9 ±12.8 and 110.6 ± 9.1, p<0.001 for both comparisons). A return to normotension comparable to baseline and control measurements was observed in experimental mice after sustained SBP elevation at 2, 4, and 6 weeks. While there was variability in the timing of the decline in between the mice, an overall elevation and decline trend was observed. Interestingly, aged female mice at 47.5 weeks showed no difference in SBP after 4-OHT administration when compared to control groups indicating age and gender as possible contributing factors to the effectivity of NRP1 as a pro-relaxant. This study offers NRP1 as an alternative and novel player in our understanding of hypertension and blood pressure homeostasis. / 2026-03-06T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/48357 |
| Date | 07 March 2024 |
| Creators | Ocampo, Gabriel Luis Bernardo |
| Contributors | Gerstenfeld, Louis C., Bielenberg, Diane R. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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