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Increased O2 consumption and positive inotropy caused by cyclic GMP reduction are not altered after L-type calcium
R J Leone1, K L Naim, P M Scholz
1Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School Piscataway 08854-5635, USA.
Abstract:
We tested the hypothesis that increased O2 consumption and inotropy after reduction of myocardial cyclic guanosine monophosphate (cGMP) are mediated through L-type calcium channels. Anesthetized, open-chest New Zealand white rabbits were divided into four groups. Hearts were exposed to control vehicle (n = 8); LY83583 (LY, 10(-3) mol/l, guanylate cyclase inhibitor, (n = 9); nifedipine (nif, 10(-4) mol/l, L-type calcium channel blocker, n = 8), or nif+LY (n = 6). Vehicle or compound was applied topically to the epicardium for 15 min. Subepicardial (EPI) blood flow increased (from 213 +/- 22 to 323 +/- 24 ml/ min/100 g) in the presence of LY, as did subendocardial (ENDO) blood flow (from 238 +/- 20 to 333 +/- 38 ml/min/ 100 g). O2 consumption increased in the presence of LY:18.0 +/- 1.0 (EPI) and 17.0 +/- 0.6 (ENDO) ml O2/min/100 g as compared with 9.5 +/- 2.0 (EPI) and 10.6 +/- 2.5 (ENDO) in the control group. The increase in O2 consumption with LY was undiminished in the presence of nif (nif+LY group 21.0 +/- 3.0 ml O2/min/100 g EPI and 22.1 +/- 3.8 ENDO). Nif alone decreased left ventricular dP/dtmax from (2,762 +/- 197 to 2,413 +/- 316 mm Hg/s) and maximal rate of change in wall thickness (dW/dtmax from 13.5 +/- 2.0 to 9.5 +/- 0.8 mm/s), while percent change of wall thickness (from 21.3 +/- 3.3 to 31.3 +/- 7.2) and dW/dtmax (from 13.3 +/- 3.0 to 15.3 +/- 2.3 mm/s) increased in the nif+LY group. Thus, the positive O2 consumption and inotropic effects of decreasing cGMP were undiminished by nif. These results suggest that the cGMP reduction induced increases in O2 consumption and that inotropy may not be mediated through L-type calcium channels.
Insights
Reducing cyclic guanosine monophosphate (cGMP) increased myocardial oxygen consumption and contractility. These effects were not mediated by L-type calcium channels, as shown by experiments using nifedipine.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Myocardial cyclic guanosine monophosphate (cGMP) plays a role in regulating cardiac function.
- L-type calcium channels are critical for cardiac contractility and oxygen consumption.
Purpose of the Study:
- To investigate whether the increased oxygen consumption and inotropy observed after reducing myocardial cGMP are mediated through L-type calcium channels.
Main Methods:
- Anesthetized open-chest New Zealand white rabbits were used.
- Hearts were treated with a guanylate cyclase inhibitor (LY83583), an L-type calcium channel blocker (nifedipine), or both.
- Myocardial blood flow, oxygen consumption, and contractility (left ventricular dP/dtmax, wall thickness changes) were measured.
Main Results:
- LY83583 administration increased subepicardial and subendocardial blood flow and oxygen consumption.
- The increase in oxygen consumption induced by LY83583 was not diminished by nifedipine.
- Nifedipine alone decreased left ventricular dP/dtmax and maximal rate of change in wall thickness, but these effects were altered in the nifedipine+LY83583 group.
Conclusions:
- Reduction of myocardial cGMP leads to increased oxygen consumption and inotropy.
- These effects are independent of L-type calcium channel activity.
- The findings suggest that cGMP reduction-induced increases in myocardial oxygen consumption and inotropy are not mediated via L-type calcium channels.