Benishin C G, Lewanczuk R Z, Pang P K
Department of Physiology, Faculty of Medicine, University of Alberta, Edmonton, Canada.
Proc Natl Acad Sci U S A. 1991 Jul 15;88(14):6372-6. doi: 10.1073/pnas.88.14.6372.
Parathyroid hypertensive factor (PHF) is a newly described hypertensive factor that may be related to elevation of blood pressure in 30-40% of North American essential hypertensive patients. PHF is also found in several animal models of hypertension, including spontaneously hypertensive rats, and deoxycorticosterone acetate salt hypertensive rats. Plasma collected from spontaneously hypertensive rats (SHR) was used in the present study for purification of PHF. Plasma was dialyzed at a molecular mass cutoff of 1 kDa, and then ultrafiltered at a molecular mass cutoff of 5 kDa. PHF activity, as determined by bioassay (characteristic delayed hypertensive response in normotensive rat) was retained in the fraction that was greater than 1 kDa and less than 5 kDa. Dialyzed and ultrafiltered SHR plasma was fractionated by molecular-exclusion chromatography, either with Bio-Gel P-6 liquid chromatography, or TSK 2000 SW HPLC. The biological activity was detected in a discrete region corresponding to a molecular mass of 2.5-3 kDa. When the molecular-exclusion fraction was subsequently fractionated by reverse-phase HPLC, biological activity was located in a single discrete peak, which did not occur in plasma from normotensive rats prepared in a similar manner. The biologically active fraction of PHF was inactivated by trypsin; this and its UV spectrum indicate the presence of a peptide structure.
甲状旁腺高血压因子（PHF）是一种新发现的高血压因子，在30%至40%的北美原发性高血压患者中，其可能与血压升高有关。在包括自发性高血压大鼠和醋酸脱氧皮质酮盐高血压大鼠在内的几种高血压动物模型中也发现了PHF。本研究使用从自发性高血压大鼠（SHR）采集的血浆来纯化PHF。血浆在分子量截留值为1 kDa时进行透析，然后在分子量截留值为5 kDa时进行超滤。通过生物测定法（正常血压大鼠典型的延迟高血压反应）测定，PHF活性保留在大于1 kDa且小于5 kDa的组分中。经透析和超滤的SHR血浆通过分子排阻色谱法进行分离，使用Bio-Gel P-6液相色谱法或TSK 2000 SW高效液相色谱法。在对应于分子量为2.5至3 kDa的离散区域检测到生物活性。当随后通过反相高效液相色谱法对分子排阻级分进行分离时，生物活性位于一个单一的离散峰中，而以类似方式制备的正常血压大鼠血浆中未出现该峰。PHF的生物活性级分被胰蛋白酶灭活；这及其紫外光谱表明存在肽结构。
