Altered Renal Hemodynamics in Mice Overexpressing the Parathyroid Hormone (PTH)/PTH-Related Peptide Type 1 Receptor in Smooth Muscle

William T. Noonan, Jin Qian, William D. Stuart, Thomas L. Clemens, John N. Lorenz

Research output: Contribution to journalArticlepeer-review

Abstract

PTH-related protein (PTHrP) is an autocrine/paracrine peptide expressed in renal tubules and vasculature and may play an important role in regulating overall renal function. To evaluate the potential role of endogenous PTHrP in the control of renal hemodynamics, we performed clearance measurements in transgenic (TG) mice in which the SMP8 α-actin promoter was used to drive overexpression of the PTH/PTHrP type 1 receptor in smooth muscle. In protocol I, responses to acute saline volume expansion (SVE, 0.75 μl/min·g body weight) were measured in TG and nontransgenic (NTG) mice. Mean arterial pressure was significantly lower in TG mice throughout the experiment, and it decreased comparably in both groups in response to SVE. SVE significantly increased effective renal plasma flow in both groups of mice, but the increase was greater in TG than in NTG. Glomerular filtration rate decreased in response to SVE in NTG but did not change in TG animals. In protocol II, renal responses to angiotensin II (ANG II) infusion were determined (0.5 ng/min·g body weight). Baseline arterial pressure was again significantly lower in TG, compared with NTG mice, and TG mice had a blunted presser response to ANG II. Also, ANG II decreased effective renal plasma flow and glomerular filtration rate in both groups of animals, but the reductions were less in TG than in NTG mice. Our findings indicate that smooth-muscle-specific overexpression of the PTH/PTHrP type 1 receptor resulted in augmentation of the vasodilatory response to SVE and attenuation of the vasoconstrictor response to ANG II. We conclude that endogenous PTHrP can act as an endogenous vasorelaxant factor to modulate renal responses to vasoactive stimuli.

Original languageEnglish (US)
Pages (from-to)4931-4938
Number of pages8
JournalEndocrinology
Volume144
Issue number11
DOIs
StatePublished - Nov 2003
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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