Abstract
With developing congestive heart failure (CHF), activation of the vasopressin V1a and angiotensin II type 1 (AT1) receptors can occur. In the present study, we examined the direct effects of V1a receptor blockade (V1a block), selective AT1 receptor blockade (AT1 block), and dual V1a/AT1receptor blockade (dual block) with respect to left ventricular (LV) function and contractility during the progression of CHF. LV and myocyte functions were examined in pigs with pacing CHF (rapid pacing, 240 beats/min, 3 weeks, n = 10), pacing CHF with concomitant V1a block (SR49059, 60 mg/kg,n = 8), pacing CHF with concomitant AT1block (irbesartan, 30 mg/kg, n = 7), or pacing CHF with dual block (n = 7). LV end-diastolic dimension and peak wall stress were reduced in all receptor blockade groups compared with CHF values. However, LV fractional shortening was increased only in the dual block group compared with CHF values (29 ± 3 versus 21 ± 2, P < .05). Basal LV myocyte percent shortening increased in the dual block group compared with CHF values (3.44 ± 0.23 versus 2.88 ± 0.11,P < .05). Although V1a or AT1 block reduced LV loading conditions, only dual block resulted in improved LV and myocyte shortening.
Footnotes
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Send reprint requests to: Francis G. Spinale, M.D., Ph.D., Cardiothoracic Surgery, Room 625, Strom Thurmond Research Bldg., 770 MUSC Complex, 114 Doughty St., Charleston, SC 29425.
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↵1 This work was supported in part by National Institutes of Health Grants HL59165 and HL57952 (F.G.S.) and an unrestricted Basic Research Grant from Sanofi-Synthelabo/Bristol Meyers-Squibb (F.G.S.). F.G.S. is an Established Investigator for the American Heart Association.
- Abbreviations:
- ACE
- angiotensin-converting enzyme
- AT1
- angiotensin II type 1
- CHS
- congestive heart failure
- LV
- left ventricular
- ANP
- atrial natriuretic peptide
- BUN
- blood urea nitrogen
- Received August 20, 1999.
- Accepted February 4, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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