Trifluoperazine Attenuation of PTH-Induced Vasodilation in the Spontaneously Hypertensive Rat

  • David A. McCarron
  • James R. Grady
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 178)


Transmembrane Ca2+ fluxes and the Ca2+-calmodulin binding have been implicated in PTH’s acute vascular effects in experimental animals. To evaluate that postulate, we determined the influence of the calmodulin inhibitor, trifluoperazine (TFP), on the acute BP response to human PTH 1-34 of 18-week-old spontaneously hypertensive rats (SHR). Human PTH 1-34 was administered intravenously at doses of either 5 or 10 pg/kg. TFP 0.1 mg/kg was then given following recovery to baseline BP. Then hPTH 1-34 (5 μg/kg or 10 μg/kg) was again administered at both land 30-minute intervals after TFP.

Human PTH 1-34 at both the 5 μg/kg (p<.005) and 10 μg/kg dose (p<.001) produced acute hypotension. The hemodynamic response was maximal at 1 minute and lasted up to 30 minutes. TFP significantly reduced the maximal (A MAP) hypotensive response for the 5 μg/kg (p<.02) and for the 10 μg/kg PTH dose (p<.02). When PTH was administered 30 minutes after TFP, the acute vasodepressive response was again inhibited in the SHRs who received the 5 μg/kg (p<.02) dose and in those who received the 10 μg/kg dose (p<.01). At the 10 μg/kg dose, TFP’s inhibition of PTH-induced vasodilation not only impaired the 1-minute maximal response, but accelerated the return to baseline blood pressure. Human PTH’s (1-34) vascular actions in the SHR appear to require the integrity of the Ca2+-calmodulin system.


Mean Arterial Pressure Baseline Blood Pressure Hypotensive Response Calmodulin Inhibitor Acute Hypotension 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    D.A. McCarron, D.H. Ellison, and S.A. Anderson, Vasodilation mediated by human PTH 1–34 in the spontaneously hypertensive rat, Am. J. Physiol. 246 (Renal Fluid Electrolyte Physiol 15): F96 - F100 (1984).PubMedGoogle Scholar
  2. 2.
    G.A. Charbon, and P.F. Hulsteart, Augmentation of arterial and hepatic blood flow by extracted and synthetic parathyroid hormone, Endocrin. 95: 621 (1974).CrossRefGoogle Scholar
  3. 3.
    M.F. Crass, and P.K.T. Pang, Parathyroid hormone: a coronary artery vasodilator, Science 217: 1087 (1980).CrossRefGoogle Scholar
  4. 4.
    A. Lindner, J.A. Tremann, J. Plantier, W. Chapman, A.W. Farrey, G. Hanes, and G.M. Palmier, Effects of parathyroid hormone on the renal circulation in unanesthetized dogs, Min. Electrol. Metab. 1: 155–165 (1978).Google Scholar
  5. 5.
    P.K.T. Pang, H.F. Janssen, and J.A. Yee, Effects of synthetic parathyroid hormone on vascular beds of dogs, Pharmacologist 217: 213 (1980).Google Scholar
  6. 6.
    P.K.T. Pang, M. Yang, C. Oguro, J.G. Phillips, and J.A. Yee, Hypotensive actions of parathyroid hormone preparations in vertebrates, Gen. Comp. Endocrinol. 41: 135–138 (1980).CrossRefGoogle Scholar
  7. 7.
    A.B. Borle, Calcium metabolism at the cellular level, Fed. Proc. 32: 1944–1950 (1973).Google Scholar
  8. 8.
    J.A. Parsons, R.M. Peer, and J.T. Polts, Initial fall of plasma calcium after intravenous injection of parathyroid hormone, Endocrin. 89: 735–740 (1971).CrossRefGoogle Scholar
  9. 9.
    H. Rasmassen, Calcium and Camp stimuli-response coupling, Ann. NY Acad. Sci. 356: 346–353 (1980).CrossRefGoogle Scholar
  10. 10.
    S.A. Anderson, J.R. Grady, D.H. Ellison, and D.A. McCarron, Ca2+ balance and parathyroid hormone-mediated vasodilation in the SHR, Hypertens. 5:I-59-I-63 (1983).Google Scholar
  11. 11.
    H. Kuriyama, Y. Ito, H. Suzuti, K. Kitamura, and T. Itoh, Factors modifying contraction-relaxation cycle in vascular smooth muscle, Am. J. Physiol. 243: H641 - H662 (1982).PubMedGoogle Scholar
  12. 12.
    H. Rasmussen, Cellular calcium metabolism, Ann. Intern. Med. 98: 809–816 (1983).PubMedGoogle Scholar
  13. 13.
    R.M. Levin, and B. Weiss, Selective binding of anti-psychotics and other psychoactive agents to the calcium-dependent activation of cyclic nucleotide phosphodiesterase, J. Pharmac. Exp. Ther. 208: 454 (1979).Google Scholar
  14. 14.
    R.M. Levin, and B. Weiss, Binding of trifluoperazine to the calcium-dependent activation of cyclic nucleotide phosphodiesterase, Molec. Pharmac. 13: 690 (1977).Google Scholar
  15. 15.
    D.H. Ellison, and D.A. McCarron, Structural prerequisites of parathyroid hormone’s hypotensive action, Am. J. Physiol. (in press).Google Scholar
  16. 16.
    P.K.T. Pang, T.E. Tenner, J.A. Yee, M. Yang, and H.F. Janseen, Hypotensive action of parathyroid hormone preparations on rats and dogs, Proc. Nat. Acad. Sci. 77: 675–678 (1980).PubMedCrossRefGoogle Scholar
  17. 17.
    R. Schleiffer, A. Berthelot, and A. Gainard, Action of parathyroid extrt on arterial pressure and on contraction and 45Ca++ exchanged in isolated aorta of the rat. Eur. J. Pharm. 58: 163–167 (1978).Google Scholar
  18. 18.
    R.V. Farese, Phosphóinositide metabolism and hormone action, Endocrin. Rev. 4: 78–95 (1983).CrossRefGoogle Scholar
  19. 19.
    M.W. Osborn, F. Kouz love, M.R. Cohen, and J.J. Wenger, Bromolasalocid (Ro 20–0006) anti-hypertensive ionophore, Fed. Proc. 42: 191–195 (1983).Google Scholar
  20. 20.
    R.L. Rubin, Calciúm-p oTholipid interactions in secretory cells: a new perspective on stimulus-secretion coupling, Fed. Proc. 41: 2181–2187 (1982).Google Scholar
  21. 21.
    L.J. VanEldik,J.G. Zendegui, D.R. Marshak, and D.M. Watterson, Calcium-binding proteins and the molecular basis for calcium action, Int. Rev. Cytol. 77: 1–51 (1982).CrossRefGoogle Scholar
  22. 22.
    C.B. Klee, and T.C. Vanaman, Calmodulin, in: “Advances in Protein Chemistry,” Academic, New Yort(1982).Google Scholar
  23. 23.
    M.A. Devynck, M.G. Penollet, A.M. Muney, and P. Meger, Analysis of calcium handling in erythrocyte membranes of genetically hypertensive rats, Hypertens. 3: 397–403 (1981).CrossRefGoogle Scholar
  24. 24.
    Y.N. Postnov, and S.N. Orlov, Evidence of altered calcium accumulation and calcium binding by the membranes of, adipocytes in spontaneously hypertensive rats, Pflugers Arch. 385: 85–89 (1980).PubMedCrossRefGoogle Scholar
  25. 25.
    Y.N. Postnov, S.N. Orlov, and N.I. Potodin, Decrease in calcium binding by red blood cell membranes in spontaneously hypertensive rats and essential hypertension, Pflugers Arch. 379: 191–195 (1979).PubMedCrossRefGoogle Scholar
  26. 26.
    R.C. Webb, and R.C. Bh Via, Altered calcium sequestration by subcellular fractions of vascular smooth muscle from spontaneously hypertensive rats, J. Molec. Cell Cardiol. 8: 651–661 (1976).CrossRefGoogle Scholar
  27. 27.
    S. Koutouzoo, P. Marche, J.F. Cloix, and P. Meyer, Phospholipid phosphorylation in erythrocyte of spontaneously hypertensive rats, Am. J. Physiol. 243 (Heart Circ Physiol 12):H641–H662(1982).Google Scholar

Copyright information

© Plenum Press, New York 1984

Authors and Affiliations

  • David A. McCarron
    • 1
  • James R. Grady
    • 1
  1. 1.Division of Nephrology/HypertensionOregon Health Sciences UniversityPortlandUSA

Personalised recommendations