Garcia R, Gauquelin G, Thibault G, Cantin M, Schiffrin E L
Laboratory of Experimental Hypertension and Vasoactive Peptides, Clinical Research Institute of Montreal, Quebec, Canada.
Hypertension. 1989 Jun;13(6 Pt 1):567-74. doi: 10.1161/01.hyp.13.6.567.
There are differences in the renal handling of sodium between spontaneously hypertensive rats (SHR) and their normotensive controls. We investigated whether this difference may be associated with changes in plasma and tissue atrial natriuretic factor (ANF) levels and with alterations in glomerular ANF receptors at 4, 8, 12, and 16 weeks of age. Age-matched Wistar-Kyoto (WKY) and Wistar rats were used as normotensive controls. Systolic blood pressure was higher in SHR at 8, 12, and 16 weeks, and cardiac hypertrophy was also present in these animals at 4 weeks. Plasma ANF C- and N-terminal concentrations were greater than in both normotensive groups at 8 and 16 weeks. ANF in the right atrium was higher in SHR than in WKY rats and identical to that in the Wistar group at 4 and 8 weeks. ANF in the left atrium was lower in SHR than in both control groups at week 12. No differences were found in ventricular ANF content. The density of glomerular ANF binding sites increased with age in WKY and Wistar rats but not in SHR. At weeks 8, 12, and 16, both normotensive groups had a higher density of binding sites than SHR, but binding site affinity was greater in SHR at weeks 8 and 12. After incubation with increasing concentrations of ANF, the production of cyclic guanosine monophosphate (cGMP) by isolated glomeruli from 16-week-old rats was lower in SHR than in both normotensive groups. We conclude that the development of hypertension in SHR is associated with higher plasma ANF levels and decreased glomerular ANF receptor density and glomerular cGMP production.(ABSTRACT TRUNCATED AT 250 WORDS)
自发性高血压大鼠(SHR)与正常血压对照大鼠在肾脏对钠的处理上存在差异。我们研究了这种差异是否与4、8、12和16周龄时血浆和组织心房利钠因子(ANF)水平的变化以及肾小球ANF受体的改变有关。年龄匹配的Wistar-Kyoto(WKY)大鼠和Wistar大鼠用作正常血压对照。SHR在8、12和16周时收缩压较高,且这些动物在4周时也出现心脏肥大。在8周和16周时,SHR血浆ANF C末端和N末端浓度均高于两个正常血压组。在4周和8周时,SHR右心房中的ANF高于WKY大鼠,与Wistar组相同。在第12周时,SHR左心房中的ANF低于两个对照组。心室ANF含量未发现差异。WKY和Wistar大鼠肾小球ANF结合位点的密度随年龄增加,而SHR则不然。在8、12和16周时,两个正常血压组的结合位点密度均高于SHR,但在8周和12周时SHR的结合位点亲和力更高。用浓度递增的ANF孵育后,16周龄大鼠分离肾小球产生的环磷酸鸟苷(cGMP)在SHR中低于两个正常血压组。我们得出结论,SHR高血压的发展与较高的血浆ANF水平、降低的肾小球ANF受体密度和肾小球cGMP产生有关。(摘要截断于250字)