Brock J A, Van Helden D F, Dosen P, Rush R A
Neuroscience Group, Faculty of Medicine and Health Sciences, University of Newcastle, Callaghan, NSW, Australia.
J Auton Nerv Syst. 1996 Nov 6;61(2):97-102. doi: 10.1016/s0165-1838(96)00063-x.
It has previously been reported that the increase in blood pressure in the spontaneously hypertensive rat (SHR) occurs concurrently with a marked increase in thickness of the arterial wall and an increase in vascular innervation, particularly for the small muscular arteries. The purpose of the present study was to determine whether prevention of the increase in vascular innervation could prevent elevation of blood pressure in the SHR. We found that intraperitoneal injection of a single dose of an antiserum to nerve growth factor (anti-NGF) into young SHRs (postnatal day 19-24) caused a marked reduction in mean blood pressure at age 3-4 months from the raised value of 24.2 +/- 0.5 kPa to 18.9 +/- 0.8 kPa. By comparison, treated Wistar Kyoto rats (WKYs) maintained normal blood pressures. The treatment reduced the amplitude of the intracellularly recorded excitatory junction potential and the NA content of mesenteric arteries in the SHR, leaving the values similar to those of control WKYs. The NA content of these vessels was also reduced in treated WKYs. Importantly, the thickness of the vessel wall, which was greater in the SHR than the WKY, was not significantly altered by anti-NGF treatment. It is concluded that anti-NGF treatment during late neonatal development inhibits the increase in the functional levels of vascular innervation observed in the SHR. Furthermore, this increase in the functional levels of vascular innervation is necessary for the development of hypertension in this rat strain.
此前已有报道称,自发性高血压大鼠(SHR)的血压升高与动脉壁厚度的显著增加以及血管神经支配的增加同时发生,特别是小肌性动脉。本研究的目的是确定预防血管神经支配的增加是否可以预防SHR的血压升高。我们发现,对幼龄SHR(出生后第19 - 24天)腹腔注射单剂量的神经生长因子抗血清(抗NGF),可使3 - 4月龄时的平均血压从升高值24.2±0.5 kPa显著降低至18.9±0.8 kPa。相比之下,接受治疗的Wistar Kyoto大鼠(WKY)维持正常血压。该治疗降低了SHR细胞内记录的兴奋性接头电位的幅度以及肠系膜动脉的去甲肾上腺素(NA)含量,使其值与对照WKY相似。接受治疗的WKY这些血管的NA含量也降低了。重要的是,SHR中比WKY更厚的血管壁厚度并未因抗NGF治疗而显著改变。结论是,在新生儿后期发育期间进行抗NGF治疗可抑制SHR中观察到的血管神经支配功能水平的增加。此外,这种血管神经支配功能水平的增加对于该大鼠品系高血压的发展是必要的。