Parathyroid hormone-related protein expression in vascular smooth muscle of spontaneously hypertensive rats: Evidence for lack of response to angiotensin II

Silvia I. Garcia, Thomas Clemens, James A. Fagin, Samuel Finkielman, Carlos J. Pirola

Research output: Contribution to journalArticle

Abstract

Objective. We studied the expression of parathyroid hormone (PTH)-related protein in vascular smooth muscle cells of spontaneously hypertensive rats (SHR) using Wistar-Kyoto (WKY) and Sprague-Dawley rats as normotensive controls. Methods. Aortae from 4- and 18-week-old SHR versus age-matched WKY and Sprague-Dawley rats were excised to obtain total RNA or smooth muscle cells. The cells were subcultured in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum, then serum-deprived for 72 h and stimulated with 0.1 μmol/l angiotensin II. PTH-related protein, c-myc and angiotensin II type 1a receptor (AT(1a)R) messenger (m)RNA levels were measured by Northern blot, using total RNA extracted by phenol/chloroform. The effects of PTH-related protein(1-34)NH2 intravenous injections on arterial blood pressure and the heart rate were studied in anesthetized SHR and WKY rats. Results. The Northern blots showed a significantly higher abundance of PTH-related protein mRNA in aortae of SHR versus WKY rats in the prehypertensive state but no significant difference in adult animals. In cultured aortic smooth muscle cells, angiotensin II induced a four- to sixfold increase in PTH-related protein mRNA levels in smooth muscle cells from normotensive animals, but failed to elicit a significant response in smooth muscle cells derived from SHR in either the prehypertensive or the hypertensive state. This lack of response to angiotensin II in SHR smooth muscle cells was not due to decreased expression or responsiveness of the AT(1a)R, since SHR smooth muscle cells had more AT(1a)R mRNA than Sprague-Dawley smooth muscle cells, and angiotensin II-induced activation of c-myc was faster and greater in smooth muscle cells derived from 4- or 18-week-old SHR than in Sprague-Dawley smooth muscle cells. In contrast, PTH-related protein(1-34)NH2 induced a long-lasting dose-dependent hypotensive and tachycardic response in both SHR and WKY rats, indicating that SHR retained responsiveness to the vasodilator. Conclusions. PTH-related protein gene expression in response to angiotensin II is impaired in SHR arteries. A deficiency in this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in this model.

Original languageEnglish (US)
Pages (from-to)1467-1474
Number of pages8
JournalJournal of Hypertension
Volume16
Issue number10
DOIs
StatePublished - 1998
Externally publishedYes

Fingerprint

Parathyroid Hormone-Related Protein
Inbred SHR Rats
Vascular Smooth Muscle
Angiotensin II
Smooth Muscle Myocytes
Angiotensin Type 1 Receptor
Inbred WKY Rats
Messenger RNA
Vasodilator Agents
Northern Blotting
Sprague Dawley Rats
Aorta
RNA
Eagles
Chloroform
Phenol
Serum
Intravenous Injections
Arterial Pressure
Arteries

Keywords

  • Angiotensin II
  • c-myc
  • Gene expression
  • Hypertension
  • Parathyroid hormone-related protein
  • Smooth muscle cells
  • Spontaneously hypertensive rats
  • Type 1 receptor

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology

Cite this

Parathyroid hormone-related protein expression in vascular smooth muscle of spontaneously hypertensive rats : Evidence for lack of response to angiotensin II. / Garcia, Silvia I.; Clemens, Thomas; Fagin, James A.; Finkielman, Samuel; Pirola, Carlos J.

In: Journal of Hypertension, Vol. 16, No. 10, 1998, p. 1467-1474.

Research output: Contribution to journalArticle

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abstract = "Objective. We studied the expression of parathyroid hormone (PTH)-related protein in vascular smooth muscle cells of spontaneously hypertensive rats (SHR) using Wistar-Kyoto (WKY) and Sprague-Dawley rats as normotensive controls. Methods. Aortae from 4- and 18-week-old SHR versus age-matched WKY and Sprague-Dawley rats were excised to obtain total RNA or smooth muscle cells. The cells were subcultured in Dulbecco's Modified Eagle's Medium containing 10{\%} fetal calf serum, then serum-deprived for 72 h and stimulated with 0.1 μmol/l angiotensin II. PTH-related protein, c-myc and angiotensin II type 1a receptor (AT(1a)R) messenger (m)RNA levels were measured by Northern blot, using total RNA extracted by phenol/chloroform. The effects of PTH-related protein(1-34)NH2 intravenous injections on arterial blood pressure and the heart rate were studied in anesthetized SHR and WKY rats. Results. The Northern blots showed a significantly higher abundance of PTH-related protein mRNA in aortae of SHR versus WKY rats in the prehypertensive state but no significant difference in adult animals. In cultured aortic smooth muscle cells, angiotensin II induced a four- to sixfold increase in PTH-related protein mRNA levels in smooth muscle cells from normotensive animals, but failed to elicit a significant response in smooth muscle cells derived from SHR in either the prehypertensive or the hypertensive state. This lack of response to angiotensin II in SHR smooth muscle cells was not due to decreased expression or responsiveness of the AT(1a)R, since SHR smooth muscle cells had more AT(1a)R mRNA than Sprague-Dawley smooth muscle cells, and angiotensin II-induced activation of c-myc was faster and greater in smooth muscle cells derived from 4- or 18-week-old SHR than in Sprague-Dawley smooth muscle cells. In contrast, PTH-related protein(1-34)NH2 induced a long-lasting dose-dependent hypotensive and tachycardic response in both SHR and WKY rats, indicating that SHR retained responsiveness to the vasodilator. Conclusions. PTH-related protein gene expression in response to angiotensin II is impaired in SHR arteries. A deficiency in this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in this model.",
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T1 - Parathyroid hormone-related protein expression in vascular smooth muscle of spontaneously hypertensive rats

T2 - Evidence for lack of response to angiotensin II

AU - Garcia, Silvia I.

AU - Clemens, Thomas

AU - Fagin, James A.

AU - Finkielman, Samuel

AU - Pirola, Carlos J.

PY - 1998

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N2 - Objective. We studied the expression of parathyroid hormone (PTH)-related protein in vascular smooth muscle cells of spontaneously hypertensive rats (SHR) using Wistar-Kyoto (WKY) and Sprague-Dawley rats as normotensive controls. Methods. Aortae from 4- and 18-week-old SHR versus age-matched WKY and Sprague-Dawley rats were excised to obtain total RNA or smooth muscle cells. The cells were subcultured in Dulbecco's Modified Eagle's Medium containing 10% fetal calf serum, then serum-deprived for 72 h and stimulated with 0.1 μmol/l angiotensin II. PTH-related protein, c-myc and angiotensin II type 1a receptor (AT(1a)R) messenger (m)RNA levels were measured by Northern blot, using total RNA extracted by phenol/chloroform. The effects of PTH-related protein(1-34)NH2 intravenous injections on arterial blood pressure and the heart rate were studied in anesthetized SHR and WKY rats. Results. The Northern blots showed a significantly higher abundance of PTH-related protein mRNA in aortae of SHR versus WKY rats in the prehypertensive state but no significant difference in adult animals. In cultured aortic smooth muscle cells, angiotensin II induced a four- to sixfold increase in PTH-related protein mRNA levels in smooth muscle cells from normotensive animals, but failed to elicit a significant response in smooth muscle cells derived from SHR in either the prehypertensive or the hypertensive state. This lack of response to angiotensin II in SHR smooth muscle cells was not due to decreased expression or responsiveness of the AT(1a)R, since SHR smooth muscle cells had more AT(1a)R mRNA than Sprague-Dawley smooth muscle cells, and angiotensin II-induced activation of c-myc was faster and greater in smooth muscle cells derived from 4- or 18-week-old SHR than in Sprague-Dawley smooth muscle cells. In contrast, PTH-related protein(1-34)NH2 induced a long-lasting dose-dependent hypotensive and tachycardic response in both SHR and WKY rats, indicating that SHR retained responsiveness to the vasodilator. Conclusions. PTH-related protein gene expression in response to angiotensin II is impaired in SHR arteries. A deficiency in this potent local vasodilator may contribute to the development and/or maintenance of arterial hypertension in this model.

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