Study Of The Effect Of Niflumic Acid On Spontaneously Hypertensive Rat Mesenteric Artery Gap Junction

Objective: To observe the regulation of niflumic acid (niflumic acid, NFA) on the mesenteric smallarteries of gap junctional communication.Methods: whole cell patch clamp observes blood vessel use1×10-4mol/L NFA on gap junctionalintercellular communication and different concentrations of NFA on mesenteric artery smooth musclecell membrane currents change from SHR(spontaneously hypertensive rat, SHR); Application ofpressure myogram observation of different concentrations of NFA on Wistar rats and SHR of mesentericsmall arteries diameter changes; Western blot to observe the expression of Cx43on Wistar rats and SHRmesenteric artery smooth muscle cells.Application of vascular segments were incubated with differentconcentrations of NFA on the changes of Cx43mRNA levels was observed by RT-PCR, in theapplication of Western blot though mesenteric small artery smooth muscle cell primary culture observedifferent concentrations of NFAto SHR mesenteric artery smooth muscle cells on the change of Cx43.Results:(1) patch clamp recording on single smooth muscle cells reached the maximum reaction time is2min, using different concentrations of NFArecord in a concentration dependent manner (P<0.01, n=8).whole cell patch clamp recording blood vessel use1×10-4mol/L NFA can reduce the inward current andblock the gap junction, which can reversible. charge and discharge cell membrane capacitance Cinputtimeis reduced from9.73MS to0.48mS, with statistical significance(P<0.05, n=6).(2) pressure myogram showed3×10-4mol/L NFAcan completely diastolic caused by PE, Wistar rats washigher than that of SHR on diastolic, with statistical significance (P<0.05, n=6).(3) Western blot results showed that SHR and Wistar rats, the expression of the third branches ofmesenteric vessels of Cx43were higher than that of the first branch vessel; comparison of SHR andWistar in rat mesenteric vascular branch at the same level, the expression of SHR Cx43was higher thanthat of Wistar rats; with statistical significance (F=1014.43, P<0.01). Small arteries incubated byRT-PCR display: treated with different concentrations of NFA compare to control group, the expressionof Cx43mRNA decreased significantly and is concentration dependent, with statistical significance(P<0.01). Primary culture of mesenteric small arterial smooth muscle cells through the Western blotdisplay control group compared to smooth muscle cells wtith different concentrations of NFA, theexpression of Cx43significantly decreased with concentration dependent, with statistical significance(F=1480.2, P<0.01).Conclusion: High blood pressure reactivity vascular lower which may be related to the expression ofgap junction protein, and NFA can reduce the smooth muscle cell communication, relaxation ofmesenteric small arteries and decrease the expression of Cx43. To sum up, presumably niflumic acid canact as gap junctions drug targets for the treatment of hypertension, as gap junctions provide certaintheoretical basis for the therapeutic target.