Monocrotaline‐Induced Pulmonary Hypertension in Wistar Rats

Markus Rey1, Patrick Hess1, Martine Clozel1

1 Actelion Pharmaceuticals, Allschwil, Switzerland
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.56
DOI:  10.1002/0471141755.ph0556s46
Online Posting Date:  September, 2009
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Pulmonary arterial hypertension (PAH) is a debilitating and often fatal disease characterized by a progressive increase in pulmonary vascular resistance that leads to right ventricular failure. Described in this unit is an in vivo model of monocrotaline‐induced pulmonary hypertension in rats that can be used to assess the effects of antihypertensive agents on pulmonary artery pressure and right ventricular hypertrophy. Curr. Protoc. Pharmacol. 46:5.56.1‐5.56.11. © 2009 by John Wiley & Sons, Inc.

Keywords: cardiac output; hemodynamic parameters; monocrotaline; pulmonary hypertension; rat

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Table of Contents

  • Reagents and Solutions
  • Commentary
  • Literature Cited
  • Figures
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Basic Protocol 1:

  • 180 to 220 g male Wistar rats (e.g., RCC Ltd.)
  • Rat chow
  • Monocrotaline (MCT; see recipe)
  • Physiological saline (0.9% NaCl; B. Braun)
  • Heparinized saline (see recipe)
  • Sodium thiobutabarbital (Inactin, Sigma‐Aldrich; see recipe)
  • HR lubricating jelly (Carter Products)
  • 2% xylocaine (lidocaine hydrochloridum anhydricum; AstraZeneca)
  • Makrolon type‐4 cages with wire mesh tops
  • Softwood bedding
  • Animal balance (XS 4001S; Mettler)
  • 1‐ml syringes with 26‐G needles
  • 0.32‐mm stainless steel wire
  • 3.5 French umbilical vessel catheter (Sherwood Medical)
  • Waterproof marker
  • DTX Plus transducers (Becton Dickinson, cat. no. 682021)
  • Three‐way stopcock (Discofix C; B. Braun)
  • Portex tubing PP25
  • Data acquisition equipment (EMKA Technologies, model no. ITF16)
  • Data acquisition software (IOX; EMKA Technologies)
  • Data reduction software (Datanalyst V2.1.017; EMKA Technologies)
  • Dell Optiplex GX 620 computer
  • Mercury sphygmomanometer (Caretek Medical, model no. MT‐3623)
  • 23‐G Luer stub adapter (Becton Dickinson)
  • Medical‐grade silicone tubing (0.508‐mm. i.d./0.9398‐mm o.d.; Sedat, cat. no. 602135;
  • Cardiomax III (Columbus Instruments)
  • Gaymar T/pump (Uno, cat. no. 18000007)
  • White Plexiglas heating tableau (Uno, cat. no. 18000021)
  • Martin ME102 diathermy unit (KLS Martin GMBH, cat. no. ME102;
  • Cold light source (KL 1500 LCD; Schott)
  • Surgical instruments: scissors, forceps, microvascular clamps, microscissors, small vessel catheter introducer
  • Silkam black silk 4/0 (B. Braun)
  • Electric shaver
  • Vacuum cleaner
  • Temperature monitoring system (Model BAT‐12; Physiotemp)
  • Cotton gauze (Longuettes)
  • Portex polythene tubing (1.57‐mm i.d./2.08‐mm o.d.; Smiths Medical ASD, cat. no. REF 800/100/240)
  • Cotton swabs
  • 0.5‐ml syringes
  • Adhesive tape
  • Analytical balance (SBC 33; Scaltec)
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Literature Cited

Literature Cited
   Clozel, M., Hess, P., Rey, M., Iglarz, M., Binkert, C., and Qiu, C. 2006. Bosentan, sildenafil, and their combination in the monocrotaline model of pulmonary hypertension in rats. Exp. Biol. Med. 231:967‐973.
   Gillespie, M.N., Olson, J.W., Reinsel, C.N., O'Connor, W.N., and Altiere, R.J. 1986. Vascular hyperresponsiveness in perfused lungs from monocrotaline‐treated rats. Am. J. Physiol. 251:H109‐H114.
   Ilkiw, R., Todorovich‐Hunter, L., Maruyama, K., Shin, J., and Rabinovitch, M. 1989. SC‐39026, a serine elastase inhibitor, prevents muscularization of peripheral arteries, suggesting a mechanism of monocrotaline‐induced pulmonary hypertension in rats. Circ. Res. 64:814‐825.
   Meyrick, B., Gamble, W., and Reid, L. 1980. Development of Crotalaria pulmonary hypertension: Hemodynamic and structural study. Am. J. Physiol. 239:H692‐H702.
   Molteni, A., Ward, W.F., Ts'ao, C.H., Port, C.D., and Solliday, N.H. 1984. Monocrotaline‐induced pulmonary endothelial dysfunction in rats. Proc. Soc. Exp. Biol. Med. 176:88‐94.
   Popesko, P. 1992. The Colour Atlas of Anatomy of Small Laboratory Animals, Vol. 2. Wolfe Publishing, London.
   Stinger, R.B., Iacopino, V.J., Alter, I., Fitzpatrick, T.M., Rose, J.C., and Kot, P.A. 1981. Catheterization of the pulmonary artery in the closed‐chest rat. J. Appl. Physiol. 51:1047‐1050.
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