Type 1 parathyroid hormone receptor expression level modulates renal tone and plasma renin activity in spontaneously hypertensive rat.
These studies examine whether PTHrP(1-36), a vasodilator, modulates BP and renal vascular resistance (RVR) in spontaneously hypertensive rat (SHR). Within the kidney of normotensive rats, PTHrP(1-36) was enriched in vessels. In vessels of SHR, PTHrP was upregulated by 40% and type 1 PTH receptor (PTH1R) was downregulated by 65% compared with normotensive rats. To investigate the role of endogenous PTHrP in the regulation of BP and RVR, SHR were subjected to somatic human (h)PTH1R gene delivery. Three weeks after a single intravenous injection of pcDNA1.1 plasmid containing the hPTH1R gene under the control of the cytomegalovirus promoter, hPTH1R mRNA was detected in all of the main organs. Within the kidney, the transgene was enriched in vessels. In the isolated perfused kidney, RVR was reduced by 23% and PTHrP(1-36)-induced vasodilation, which is depressed in SHR, was restored and a vasoconstrictory response to PTH(3-34), a PTH1R antagonist, was revealed. These effects were not observed in control SHR treated with empty plasmid. BP remained unchanged, and plasma renin activity increased by 60%. Thus, in SHR renal vessels, a reduced number of PTH1R contributes to the high RVR, despite the higher expression of vasodilatory PTHrP. Moreover, these studies provide evidence for a direct link between the density of PTH1R and plasma renin activity, which might be responsible for the absence of effect of PTH1R gene delivery on BP in SHR. Overall, PTHrP significantly contributes to the homeostasis of renal and systemic hemodynamics in SHR.
Massfelder
Thierry
T
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Taesch
Nathalie
N
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Fritsch
Samuel
S
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Eichinger
Anne
A
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Barthelmebs
Mariette
M
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Stewart
Andrew F
AF
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
Helwig
Jean-Jacques
JJ
*Section of Renovascular Pharmacology and Physiology (INSERM-ULP), University Louis Pasteur School of Medicine, Strasbourg, France; and Division of Endocrinology and Metabolism, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D018014:Gene Transfer Techniques; D006801:Humans; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR / Q000502:physiology*; D011921:Rats, Inbred WKY; D018016:Receptors, Parathyroid Hormone / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D012079:Renal Circulation / Q000502:physiology*; D012083:Renin / Q000097:blood*; D014655:Vascular Resistance / Q000502:physiology; D014664:Vasodilation / Q000502:physiology; D014666:Vasomotor System / Q000502:physiology*
D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D011506:Proteins; D018016:Receptors, Parathyroid Hormone; C079957:parathyroid hormone-related peptide (1-36); D012083:Renin