Modulation of renin-angiotensin and kallikrein gene expression in experimental hypertension.

Abstract

Previous studies have shown that chronic lowdose administration of 40 ng/min angiotensin II by osmotic minipump to uninephrectomized rats mimics the temporal hypertensive response and the circulating angiotensin II levels observed in two-kidney, one clip Goldblatt rats. Furthermore, renal tissue angiotensin II contents were higher than the circulating angiotensin II levels, suggesting that circulating angiotensin II induces endogenous intrarenal angiotensin II production. The present study examined the molecular mechanisms by which intrarenal angiotensin II production is modulated in angiotensin H-induced and two-kidney Goldblatt hypertension. Two weeks after clipping, intrarenal renin mRNA levels were elevated threefold in the clipped kidney of Goldblatt rats but were markedly suppressed in the nonclipped kidneys of Goldblatt rats (28% of control values) and in the remaining kidney of uninephrectomized angiotensin II-infused rats (7% of control values). In contrast, there were sustained levels of angiotensinogen mRNA in the kidneys and livers of Goldblatt and angiotensin II-infused rats, indicating differential regulation of the genes of the renin-angiotensin system. Renal kallikrein gene expression was not altered in either of the hypertensive groups 14 days after the induction of hypertension, suggesting the absence of an enhanced counteracting kinin influence.

The Effect of Isoprenaline Infusion on Renal Renin and Angiotensinogen Gene Expression in the Anaesthetised Rat

“…Moreover, there is no evidence that RPP influences AGT gene expression in the kidney even in a chronic situation (e.g. in 2K-1C Goldblatt hypertensive rats following renal artery clipping; Morishita et al 1991;Von-Thun et al 1994), although it was raised following exposure of animals to a low dietary sodium intake (Wang et al 1993;Singh et al 1996). However, it was evident that electrical stimulation of the renal sympathetic nerves at levels causing minor changes in renal haemodynamics do stimulate renal AGT mRNA levels (Nakamura & Johns, 1994.…”

Regulation of Angiotensin II Type 1 Receptor mRNA and Protein in Angiotensin II–Induced Hypertension

“…Blots were prehybridized for 1 hour at 46°C with 5ϫ SSC, 1ϫ Denhardt's solution, 0.05 mol/L PO 4 buffer (pH6.7), 2 mg denatured herring sperm DNA, 0.10 mmol/L dextran sulfate, and 50% formamide. Blots were hybridized overnight with 10 7 cpm/mL oligo probe for AT 1A and GAPDH using 5ϫ SSC, 0.5ϫ Denhardt's solution, 0.02 M PO 4 …”

“…4 Blots were hybridized to the AT 1A oligo probe and rehybridized with a GAPDH oligo probe to account for loading variations (2 to 3 months allowed for 32 P decay). Signals were detected by autoradiography and quantified by scanning laser densitometry (Ultroscan; Pharmacia LKB).…”

“…We previously demonstrated that chronic infusion of initially a subpressor dose of Ang II into uninephrectomized rats produces a slowly developing hypertension that is associated with diminished renal renin content and mRNA, enhanced renal ACE activity, maintained renal and hepatic angiotensinogen mRNA levels, and an AT 1 -mediated augmentation of intrarenal Ang II content. [1][2][3][4] However, the contribution of the expression of the AT 1 receptor to the hypertensinogenic effect of Ang II has not been established. Because most of the hypertensinogenic actions of the renin-angiotensin system are mediated by the binding of Ang II to the AT 1 receptor, the predominant receptor subtype in adult animals, and the availability of AT 1 receptors essentially determines the efficacy of the renin-angiotensin system, we studied the tissue-specific expression of the AT 1 receptor after chronic low-dose infusions of Ang II in the rat.…”

Ontogeny of the intrarenal kallikrein-kinin system: Proposed role in renal development

“…Insulin-like growth factor also stimulates kallikrein gene expression in the rat kidney . Expression of the renal kallikrein gene is suppressed in obstructive nephropathy and in the chronic phase of renovascular hypertension (El-Dahr et al, 1993a,b;Von Thun et al, 1994). Corticosteroids downregulate pancreatic kallikrein gene expression (Rosewicz et al, 1991) and renal kallikrein synthesis (Jaffa et al, 1990).…”