Isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection

Anne A. Wooldridge the Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Search for other papers by Anne A. Wooldridge in
Current site
Google Scholar
PubMed
Close
 DVM, PhD
,
A. Ray Dillon the Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Search for other papers by A. Ray Dillon in
Current site
Google Scholar
PubMed
Close
 DVM, MS, MBA
,
D. Michael Tillson the Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Search for other papers by D. Michael Tillson in
Current site
Google Scholar
PubMed
Close
 DVM, MS
,
Qiao Zhong the Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Search for other papers by Qiao Zhong in
Current site
Google Scholar
PubMed
Close
, and
Sharron R. Barney the Department of Clinical Sciences, College of Veterinary Medicine, Auburn University, Auburn, AL 36849.

Search for other papers by Sharron R. Barney in
Current site
Google Scholar
PubMed
Close

Abstract

Objective—To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection.

Animals—13 purpose-bred adult cats.

Procedures—Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10μM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10μM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P.

Results—Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged.

Conclusions and Clinical Relevance—Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.

Abstract

Objective—To determine the isometric responses of isolated intrapulmonary bronchioles from cats with and without adult heartworm infection.

Animals—13 purpose-bred adult cats.

Procedures—Cats were infected with 100 third-stage larvae or received a sham inoculation, and the left caudal lung lobe was collected 278 to 299 days after infection. Isometric responses of intrapulmonary bronchiolar rings were studied by use of a wire myograph. Three cycles of contractions induced by administration of 10μM acetylcholine were followed by administration of the contractile agonists acetylcholine, histamine, and 5-hydroxy-tryptamine. To evaluate relaxation, intrapulmonary bronchiolar rings were constricted by administration of 10μM 5-hydroxytryptamine, and concentration-response curves were generated from administration of sodium nitroprusside, isoproterenol, and substance P.

Results—Compared with tissues from control cats, contractile responses to acetylcholine and 5-hydroxytryptamine were reduced in tissues from heartworm-infected cats. Relaxation to isoproterenol was significantly reduced in tissues from heartworm-infected cats. Relaxation to substance P was increased in tissues from heartworm-infected cats, but relaxation to sodium nitroprusside was unchanged.

Conclusions and Clinical Relevance—Results suggested that despite increased bronchiolar wall thickness in heartworm-infected cats, a hyperreactive response of the bronchiolar smooth muscle is not the primary mechanism of respiratory tract clinical signs. Reduced response of the airway to isoproterenol may indicate refractoriness to bronchiolar relaxation in heartworm-infected cats.

Contributor Notes

Supported by IDEXX Corporation.

Presented in abstract form at the American College of Veterinary Internal Medicine Forum, Montreal, June 2009, and the American Heartworm Society Meeting, Memphis, April 2010.

Address correspondence to Dr. Dillon (dilloar@auburn.edu).
  • 1.

    Blagburn BL, Dillon AR. Feline heartworm disease: solving the puzzle. Vet Med 2007;(suppl):714.

  • 2.

    Dillon AR, Robertson C, Brawner B, et al. Feline heartworm disease: correlations of clinical signs, serology, and other diagnostics: results of a mulitcenter clinical study. Vet Ther 2000; 1:176182.

    • Search Google Scholar
    • Export Citation
  • 3.

    Browne LE, Carter TD, Levy JK, et al. Pulmonary arterial disease in cats seropositive for Dirofilaria immitis but lacking adult heart-worms in the heart and lungs. Am J Vet Res 2005; 66:15441549.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Dillon AR. Heartworm infection in cats: redefining the disease. Vet Forum 2008; 25:58.

  • 5.

    Litster AL, Atwell RB. Feline heartworm disease: a clinical review. J Feline Med Surg 2008; 10:137144.

  • 6.

    Mitchell RW, Ndukwu IM, Leff AR, et al. Muscarinic hyperre-sponsiveness of antigen-sensitized feline airway smooth muscle in vitro. Am J Vet Res 1997; 58:672676.

    • Search Google Scholar
    • Export Citation
  • 7.

    Padrid P, Snook S, Finucane T, et al. Persistent airway hyper-responsiveness and histologic alterations after chronic antigen challenge in cats. Am J Respir Crit Care Med 1995; 151:184193.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Schooley EK, McGee Turner JB, Jiji RD, et al. Effects of cyproheptadine and cetirizine on eosinophilic airway inflammation in cats with experimentally induced asthma. Am J Vet Res 2007; 68:12651271.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Krane CM, Fortner CN, Hand AR, et al. Aquaporin 5-deficient mouse lungs are hyperresponsive to cholinergic stimulation. Proc Natl Acad Sci U S A 2001; 98:1411414119.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Liu JQ, Yang D, Folz RJ. A novel bronchial ring bioassay for the evaluation of small airway smooth muscle function in mice. Am J Physiol Lung Cell Mol Physiol 2006; 291:L281L288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    McGraw DW, Forbes SL, Kramer LA, et al. Transgenic overex-pression of beta(2)-adrenergic receptors in airway smooth muscle alters myocyte function and ablates bronchial hyperreactivity J Biol Chem 1999; 274:3224132247.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Lorenz JN, Loreaux EL, Dostanic-Larson I, et al. ACTH-induced hypertension is dependent on the ouabain-binding site of the alpha2-Na+-K+-ATPase subunit. Am J Physiol Heart Circ Physiol 2008; 295:H273H280.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Wooldridge AA, Fortner CN, Lontay B, et al. Deletion of the protein kinase A/protein kinase G target SMTNL1 promotes an exercise-adapted phenotype in vascular smooth muscle. J Biol Chem 2008; 283:1185011859.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Brawner B, Dillon AR, Robertson C, et al. Radiographic diagnosis of feline heartworm disease and correlation to clinical criteria: results of a multicenter clinical case study. Vet Ther 2000; 1:8187.

    • Search Google Scholar
    • Export Citation
  • 15.

    Robertson C, Dillon AR, Brawner B, et al. Prevalence of feline heartworm infections among cats with respiratory and gastrointestinal signs. Vet Ther 2000; 1:8895.

    • Search Google Scholar
    • Export Citation
  • 16.

    Altiere RJ & Diamond L. Relaxation of cat tracheobronchial and pulmonary arterial smooth muscle by vasoactive intestinal pep-tide: lack of influence by peptidase inhibitors. Br J Pharmacol 1984; 82:321328.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Imoto A, Yoshida M, Takahashi N, et al. Possible role of cAMP, cGMP and [Ca2+]i during NANC relaxation in the cat airway smooth muscle. J Auton Nerv Syst 1998; 68:113.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 18.

    Padrid PA, Mitchell RW, Ndukwu IM, et al. Cyproheptadine-induced attenuation of type-I immediate-hypersensitivity reactions of airway smooth muscle from immune-sensitized cats. Am J Vet Res 1995; 56:109115.

    • Search Google Scholar
    • Export Citation
  • 19.

    Van de Voorde J & Joos G. Regionally different influence of contractile agonists on isolated rat airway segments. Respir Physiol 1998; 112:185194.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Mohammed SP, Higenbottam TW, Adcock JJ. Effects of aerosol-applied capsaicin, histamine and prostaglandin E2 on airway sensory receptors of anaesthetized cats. J Physiol 1993; 469:5166.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Chand N & Eyre P. Atypical (relaxant) response to histamine in cat bronchus. Agents Actions 1977; 7:183190.

  • 22.

    Artwohl J, Brown P, Corning B, et al. Report of the ACLAM Task Force on Rodent Euthanasia. J Am Assoc Lab Anim Sci 2006; 45:98105.

  • 23.

    Ito Y & Hakoda H. Modulation of cholinergic neurotransmission by VIP, VIP-antiserum and VIP-antagonists in dog and cat trachea: VIP plays a role of “double braking” in broncho-constriction. Agents Actions Suppl 1990; 31:197203.

    • Search Google Scholar
    • Export Citation
  • 24.

    Ito Y & Takeda K. Non-adrenergic inhibitory nerves and putative transmitters in the smooth muscle of cat trachea. J Physiol 1982; 330:497511.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 25.

    Matsumoto N, Inoue H, Ichinose M, et al. Effective sites by sympathetic beta-adrenergic and vagal nonadrenergic inhibitory stimulation in constricted airways. Am Rev Respir Dis 1985; 132:11131117.

    • Search Google Scholar
    • Export Citation
  • 26.

    Jing L, Inoue R, Tashiro K, et al. Role of nitric oxide in non-adrenergic, non-cholinergic relaxation and modulation of excitatory neuroeffector transmission in the cat airway. J Physiol 1995; 483:225237.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Fortner CN, Breyer RM, Paul RJ. EP2 receptors mediate airway relaxation to substance P, ATP, and PGE2. Am J Physiol Lung Cell Mol Physiol 2001; 281:L469L474.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 28.

    Mhanna MJ, Dreshaj IA, Haxhiu MA, et al. Mechanism for substance P-induced relaxation of precontracted airway smooth muscle during development. Am J Physiol Lung Cell Mol Physiol 1999; 276:L51L56.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Morchon R, Roca F, Lopez-Belmonte J, et al. Changes in the levels of eicosanoids in cats naturally and experimentally infected with Dirofilaria immitis. Vet Parasitol 2007; 147:271275.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Lewis SJ, Hoque A, Walton TM, et al. Potential role of nitration and oxidation reactions in the effects of peroxynitrite on the function of beta-adrenoceptor sub-types in the rat. Eur J Pharmacol 2005; 518:187194.

    • Crossref
    • Search Google Scholar
    • Export Citation

Advertisement