Hemodynamic Response of Conscious Rats and Dogs to the Protein Kinase C Inhibitor Staurosporine

  • R. Allan Buchholz
  • Ronald L. Dundore
  • Paul J. Silver
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 308)


Agonist-induced contraction of vascular smooth muscle appears to be mediated by Cat2+ influx through voltage dependent and independent channels and by receptor-linked, G-protein coupled activation of phospholipase C (1). Two intracellular messengers, inositol trisphosphate (IP3) and diacylglycerol (DAG), are generated by phospholipase C catalyzed hydrolysis of inositol bisphosphate (2). Considerable biochemical and physiological evidence suggests that IP3-mediated mobilization of intracellular Ca2+ results in calcium-regulated phosphorylation of the 20,000 dalton myosin light chain and the initiation of smooth muscle contraction (3–5). However, the mechanism(s) responsible for sustaining isometric force in vascular smooth muscle are not fully understood. Several mechanisms have been proposed for the maintenance of smooth muscle tension, including the “latch bridge” state (6) and DAG activation of protein kinase C (PKC) (7). Evidence supporting the role of PKC in the maintenance of smooth muscle tone is further reviewed in an earlier chapter (8). Staurosporine has been identified as a very potent PKC inhibitor (9). The cardiovascular actions of staurosporine in vivo have not been fully characterized. Therefore, we examined the hemodynamic response to staurosporine in conscious, spontaneously hypertensive rats (SHR) and conscious normotensive dogs.


Mean Arterial Pressure Renal Blood Flow Myosin Light Chain Kinase Inositol Trisphosphate Total Peripheral Vascular Resistance 
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.
    Nishimura J, Khalil RA, van Breeman C. Agonist-induced vascular tone. Hypertension 13: 835, 1989.PubMedGoogle Scholar
  2. 2.
    Berridge MJ. Inositol trisphosphate and diacylglycerol: Two interacting second messengers. Ann Rev Biochem 56: 159, 1987.CrossRefGoogle Scholar
  3. 3.
    Kamm KE, Stull JT. The function of myosin and myosin light chain kinase phosphorylation in smooth muscle. Ann Rev Pharmacol Toxicol 25: 593, 1985.CrossRefGoogle Scholar
  4. 4.
    Kamm KE, Stull JT. Regulation of smooth muscle contractile elements by second messengers. Ann Rev Physiol 51: 299. 1989.CrossRefGoogle Scholar
  5. 5.
    Moreland RS, Cilea J, Moreland S. Calcium and phosphorylation dependent regulation of vascular smooth muscle contraction. In: Cellular and Molecular Mechanisms of Hypertension,R.H. Cox (ed). New York: Plenum Publishing, (in press), 1990.Google Scholar
  6. 6.
    Hai CM, Murphy RA. Cat+, crossbridge phosphorylation, and contraction. Ann Rev Physiol 51: 285, 1989.CrossRefGoogle Scholar
  7. 7.
    Rasmussen H, Takuwa Y, Park S. Protein kinase C in the regulation of smooth muscle contraction. FASEB J 1: 177, 1987.PubMedGoogle Scholar
  8. 8.
    Silver PJ, Pagani ED, Cumiskey WR, Dundore RL, Harris AL, Lee KC, Ezrin AM, Buchholz RA. Calcium-regulated protein kinases and low K71 cGMP phosphodiesterases: Targets for novel antihypertensive therapy. In: Cellular and Molecular Mechanisms of Hypertension,R.H. Cox (ed). New York: Plenum Publishing, (in press), 1990.Google Scholar
  9. 9.
    Tamaoki T, Nomoto H, Takahashi I, Kato Y, Morimoto M, Tornita F. Staurosporine, a potent inhibitor of phospholipid/Ca++ dependent protein kinase. Biochem Biophys Res Commun 135: 397, 1986.PubMedCrossRefGoogle Scholar
  10. 10.
    Buchholz RA, Nathan MA. Chronic lability of the arterial blood pressure produced by electrolytic lesions of the nucleus tractus solitarii in the rat. Circ Res 54: 227, 1984.PubMedGoogle Scholar
  11. 11.
    Murakawa K, Kohno M, Yasunari K, Yokokawa K, Horio T, Takeda T. Possible involvement of protein kinase C in the maintenance of hypertension in spontaneously hypertensive rats. J Hypertension 6 (suppl 4): S157, 1988.Google Scholar
  12. 12.
    Takaori K, Itoh S, Kanayama Y, Takeda T. Protein kinase C activity in platelets from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY). Biochem Biophys Res Commun 141: 769, 1986.PubMedCrossRefGoogle Scholar
  13. 13.
    Laher I, Bevan JA. Staurosporine, a protein kinase C inhibitor, attenuates Cat+-dependent stretch-induced vascular tone. Biochem Biophys Res Commun 158: 58, 1989.PubMedCrossRefGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • R. Allan Buchholz
    • 1
  • Ronald L. Dundore
    • 1
  • Paul J. Silver
    • 1
  1. 1.Department of Cardiovascular PharmacologySterling Research GroupRensselaerUSA

Personalised recommendations