Vazopresin i neurokardiogene karakteristike hiperadrenergičkog stanja kod granično hipertenzivnih pacova
Vasopressin and neurocardiogenic characteristics in hyperadrenergic state of borderline hypertensive rats
Doktorand
Stevanović, BojanaMentor
Japundžić-Žigon, NinaČlanovi komisije
Stanković, MarijaMilutinović-Smiljanić, Sanja
Bajić, Dragana
Metapodaci
Prikaz svih podataka o disertacijiSažetak
Vazopresin (VP) je važan regulator osmotske i kardiovaskularne ravnoteže. Međutim, brojna istraživanja sugerišu da ima ulogu i u nastanku primarne hipertenzije. U ovoj studiji ispitivana je promena ekspresije gena za VP, V1a i V1b receptore (V1aR i V1bR) u paraventrikularnom jedru (PVN) hipotalamusa kao i neurokardiogene karakteristike granično hipertenzivnih pacova (BHR). U eksperimente su uključeni 12 nedelja stari mužjaci BHR soja i zdravih parnjaka Wistar pacova (WR) kao kontrole, kojima je prethodno ugrađen transmiter u aortu, za registrovanje krvnog pritiska (BP). Svi pacovi su raspoređeni metodom slučajnog izbora u četiri eksperimentalne grupe: 1) WR pod bazalnim uslovima; 2) BHR-ovi pod bazalnim uslovima; 3) BHR-ovi opterećeni solju; 4) BHR-ovi opterećeni solju i izloženi stresu. Neurokardiogeni parametri određeni su metodom spektralne analize BP-a i srčane frekvencije (HR), a senzitivnost barorefleksa (BRS) metodom sekvenci. Koncentracija VP-a u plazmi merena je radioimunoesej...om (RIA). Nivo ekspresije gena za VP, V1aR i V1bR utvrđen je metodom RT-qPCR-a. Pod bazalnim uslovima BHR-ovi su imali povećanu ekspresiju gena za VP i V1bR u PVN-u, povišenu koncentraciju VP-a u plazmi, kao i porast BRS-a u odnosu na kontrole. Opterećenje BHR-ova solju dovelo je do smanjenja ekspresije gena za V1bR i opadanja vrednosti HR-a, u odnosu na bazalne uslove. Dodatno izlaganje stresu povećalo je BP i spektralne simpatičke markere. Istovremeno kod ovih pacova HR i VP u plazmi su se smanjili u odnosu na kontrolne vrednosti. Ovi rezultati sugerišu da je povećanje genske ekspresije za VP i V1bR u PVN-u konstitutivna karakteristika BHR-ova i da nema ulogu u nastanku hipertenzije indukovane stresom.
Vasopressin is a well-recognized regulator of osmotic and cardiovascular homeostasis. However, numerous results suggest its role in development of primary hypertension. In this study we investigated gene expression of VP, and its receptors (V1aR i V1bR) in paraventricular nucleus (PVN) of hypothalamus, as well as neurocardiogenic characteristics of borderline hypertensive rats (BHR). Experiments included 12 weeks old BHR males, which were age-matched with normotensive WR controls. All animals were equipped with aorta-implanted radiotelemetry devices for continuous blood pressure (BP) measurements, and randomized in four experimental groups: 1) WRs under baseline conditions; 2) BHRs under baseline conditions; 3) salt-loaded BHRs; 4) salt-loaded plus stressed BHRs. Neurocardiogenic parameters were assessed by spectral analysis of BP and heart rate (HR), whereas baroreflex sensitivity (BRS) was analyzed by sequence method. Plasma VP was determined using radioimmunoassay (RIA). Expression ...of VP, V1aR and V1bR genes was determined by RT-qPCR. BHRs under baseline conditions had overexpression of VP and V1bR genes in the PVN, elevated plasma VP levels followed by increase in BRS compared with controls. Salt-loading of BHRs reduced expression of V1bR gene, as well as HR, compared to baseline conditions. Adding stress to salt-loading increased BP and spectral sympathetic markers in BHRs. Also, these animals exhibited lower HR and plasma VP concentrations compared to baseline conditions. These results suggest that elevated expression of VP and V1bR genes is a constitutive trait of BHRs, and is not a mechanism responsible for development of stress induced hypertension.
Fakultet:
Универзитет у Београду, Медицински факултетDatum odbrane:
11-06-2021Projekti:
- Funkcionalna genomika hipotalamusa i medule u hipertenziji indukovanoj hroničnim stresom (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41013)