P-357: Replenishment of PTH1 receptor pool by peripheral receptor gene delivery in spontaneously hypertensive rats (SHR) does not affect blood pressure but increases plasma renin activity

• Published in: American journal of hypertension 2001-04, Vol.14 (S1), p.150A-150A
• Main Authors: Fritsch, Samuel, Massfelder, Thierry, Grima, Michèle, Teasch, Nathalie, Eichinger, Anne, Escande, Benoit, Barthelmebs, Mariette, Helwig, Jean-Jacques
• Format: Article
• Language: English
• Subjects: parathyroid hormone-related protein (PTHrP); plasma renin activity; renal vessels
• ISSN: 0895-7061; 1941-7225; 1879-1905
• DOI: 10.1016/S0895-7061(01)01953-7

In a parallel abstract, Massfelder et al. provide evidence for downregulation of PTH1 receptor (PTH1R) and upregulation of dilatory PTH-related protein (PTHrP) in intrarenal arteries of SHR. Replenishment of renal vessels with PTH1R by intravenous human (h)PTH1R gene delivery, decreased SHR renal vascular tone in vitro, owing to endogenous PTHrP. These observations suggested potential therapeutic effects of somatic hPTH1R gene delivery to decrease blood pressure in SHR. To test this possibility, hPTH1R DNA (1.9 kb) under the control of the cytomegalovirus promoter in the pcDNA1.1 vector was generated. The naked DNA (0.5mg) construct was delivered into SHR via a single intravenous injection. Control-treated SHR received 0.5mg empty vector. As reported in the parallel abstract, 3 weeks after injection, the expression of hPTH1R mRNA was identified in all main organs, including hearth, aorta and intrarenal arteries. Systolic blood pressure (SBP) was measured blindly in control- and PTH1R-transfected SHR, by the sphygmomanometric tail-cuff method. SBP was not affected in hPTH1R-transfected SHR (n=12) as compared to controls (n=12), before (210±6 vs. 210±10 mmHg), as well as 7 (239±13 vs. 218±10 mmHg) and 14 days (224±10 vs. 238±12 mmHg) after plasmid injection. We previously reported that PTHrP directly interacts with juxtaglomerular cells to stimulate renin release. We therefore hypothesized that the absence of effect of PTH1R gene delivery on SBP, despite the overexpression of vascular PTHrP, was due to the simultaneous activation of the renin-angiotensin system. To test this hypothesis, plasma renin activity (PRA) was measured before, as well as 1, 4, 7, 10, 14 and 18 days following plasmid injection in PTH1R-transfected SHR (n=5), as compared to control SHR(n=5). PRA was expressed as ng immunoreactive angiotensin-I generated from rat angiotensinogen per mg protein and during 1hr incubation with converting enzyme inhibitors. PRA was not significantly different before, as well as 1 and 4 days after plasmid injection. On the other hand, PRA significantly increased (p