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alpha 1‐adrenoceptor‐mediated negative inotropy of adrenaline in rat myocardium.
Author(s) -
Kissling G,
Blickle B,
Ross C,
Pascht U,
Gulbins E
Publication year - 1997
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1997.sp021920
Subject(s) - inotrope , adrenergic receptor , medicine , beta adrenoceptor , endocrinology , contractility , chemistry , receptor
1. The effect of alpha‐ and beta‐adrenoceptor stimulation on isotonic contraction was investigated on right ventricular papillary muscles of the rat, stimulated at a rate of 0.5 Hz. 2. Adrenaline (0.5 microM) induced a slight but significant negative inotropic effect: shortening decreased from 0.137 +/‐ 0.058 to 0.122 +/‐ 0.059 muscle lengths (mean +/‐ S.D.; ‐11%, P < 0.0001) and maximum shortening velocity from 2.9 +/‐ 1.2 to 2.7 +/‐ 1.3 muscle lengths s‐1 (‐7%, P < 0.025). 3. The negative inotropic effect of adrenaline was enhanced after blocking the beta‐adrenoceptors with 50 microM atenolol. On the other hand, exposure to adrenaline after blocking the alpha‐adrenoceptors with 50 microM phentolamine resulted in an increase in shortening as well as in maximum shortening velocity. 4. Stimulation of the beta‐adrenoceptors with 0.5 microM isoprenaline caused marked positive inotropic effects, whereas stimulation of the alpha 1‐adrenoceptors with 0.5 microM phenylephrine regularly resulted in a long‐lasting decrease in shortening and maximum shortening velocity. 5. 1,2‐Dioctanoyl‐sn‐glycerol (1,2‐DOG) and adrenaline induced an activation of protein kinase C (PKC) with translocation of this enzyme from the cytosol to the sarcolemma. 6. Activation of PKC with 10 microM 1,2‐DOG and 0.5 microM adrenaline was accompanied by a decrease in shortening and maximum shortening velocity. Inhibition of PKC with 0.1 microM staurosporine abolished the negative inotropic effect of adrenaline. 7. From these results we conclude that a low dose of adrenaline stimulates not only beta‐but also alpha‐adrenoceptors and that the observed negative inotropic effect of adrenaline is mediated by alpha 1‐adrenoceptors, linked to the diacylglycerol‐PKC signal transduction pathway.