Trifluoperazine Attenuation of PTH-Induced Vasodilation in the Spontaneously Hypertensive Rat
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.
KeywordsMean Arterial Pressure Baseline Blood Pressure Hypotensive Response Calmodulin Inhibitor Acute Hypotension
Unable to display preview. Download preview PDF.
- 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.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
- 7.A.B. Borle, Calcium metabolism at the cellular level, Fed. Proc. 32: 1944–1950 (1973).Google Scholar
- 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
- 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.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.D.H. Ellison, and D.A. McCarron, Structural prerequisites of parathyroid hormone’s hypotensive action, Am. J. Physiol. (in press).Google Scholar
- 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
- 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.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
- 22.C.B. Klee, and T.C. Vanaman, Calmodulin, in: “Advances in Protein Chemistry,” Academic, New Yort(1982).Google Scholar
- 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