![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
NC Trippodo, M Fox, V Natarajan, BC Panchal, CR Dorso and MM Asaad
Department of Pharmacology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey.
Inhibition of the metallopeptidase neutral endopeptidase 3.4.24.11 (NEP) protects endogenous natriuretic peptides and potentiates their vasodepressor effects. Inhibition of angiotensin converting enzyme (ACE) attenuates the formation of angiotensin II and enhances the vasodepressor effect of endogenous kinins. A combination of NEP inhibition and ACE inhibition can potentially interact to shift the balance of vasoactive peptides toward vasodilation. This potential interaction was examined in conscious cardiomyopathic hamsters with low cardiac output and compensated heart failure. Neither the selective NEP inhibitor SQ 28,603 nor the selective ACE inhibitor enalaprilat (each at 30 mumol/kg, i.v.) caused significant changes in left ventricular end diastolic pressure or left ventricular systolic pressure when administered separately. However, the combination of these inhibitors, each at that dose, caused significant peak decreases in left ventricular end diastolic pressure and left ventricular systolic pressure of -12 +/- 1 and -18 +/- 4 mm Hg, respectively. In separate cardiomyopathic hamsters, this same combination of treatments resulted in significant decreases in mean arterial pressure (-13%) and total peripheral resistance (-37%) and an increase in cardiac output (36%) as compared with vehicle effects (P < .05). At 90 min after administration of SQ 28,603 alone, plasma atrial natriuretic peptide concentration was double that in the vehicle group. In the group receiving the combination of inhibitors, plasma atrial natriuretic peptide at 90 min was maintained at the high basal levels associated with this model despite the decrease in cardiac filling pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
This article has been cited by other articles:
|
|
 |
|
  L. M. Burrell, N. K. Farina, L. C. Balding, and C. I. Johnston Beneficial Renal and Cardiac Effects of Vasopeptidase Inhibition With S21402 in Heart Failure Hypertension, December 1, 2000; 36(6): 1105 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Raut, J.-L. Rouleau, C. Blais Jr., H. Gosselin, G. Molinaro, M. G. Sirois, Y. Lepage, P. Crine, and A. Adam Bradykinin metabolism in the postinfarcted rat heart: role of ACE and neutral endopeptidase 24.11 Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1769 - H1779. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Marie, C. Mossiat, C. Gros, J.-C. Schwartz, J.-M. Lecomte, and J. Bralet Effect of long-term therapy with fasidotril, a mixed inhibitor of neprilysin and angiotensin-converting enzyme (ACE), on survival of rats after myocardial infarction Cardiovasc Res, March 1, 1999; 41(3): 544 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. A. Gutierrez, S. G. Clark, A. D. Giulumian, and L. C. Fuchs Superoxide Anions Contribute to Impaired Regulation of Blood Pressure by Nitric Oxide During the Development of Cardiomyopathy J. Pharmacol. Exp. Ther., September 1, 1997; 282(3): 1643 - 1649. [Abstract] [Full Text]
|
|
|
|
|
|
J. G. Motwani, C. C. Lang, G. Cramb, and A. D. Struthers Natriuretic Response to Neutral Endopeptidase Inhibition Is Blunted by Enalapril in Healthy Men Hypertension, April 1, 1995; 25(4): 637 - 642. [Abstract] [Full Text]
|
|
|
|
 |
|
 H. H. Chen, J. G. Lainchbury, G. J. Harty, and J. C. Burnett Jr Maximizing the Natriuretic Peptide System in Experimental Heart Failure: Subcutaneous Brain Natriuretic Peptide and Acute Vasopeptidase Inhibition Circulation, February 26, 2002; 105(8): 999 - 1003. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
