Sensitivity of cardiac tissues with moderate and advanced hypertrophy to calcium ions.
1. Prolonged existence of hypertension is known to induce a compensatory increase in cardiac weight, later followed by a loss of functional responsiveness to biological stimuli. 2. It was the aim of the present study to investigate the functional responses of hypertrophied hearts to rising levels of intracellular calcium. The experiments were performed using two different degrees of cardiac hypertrophy, the first as obtained in spontaneously hypertensive rats (SHR) of 18-20 weeks old, the second by using rats, 32-34 weeks old, with a surgically induced stenosis of the thoracic aorta (ASR). The ASR, which showed signs of overt heart failure, may be presented as a model for hypertension-induced end-stage cardiac hypertrophy. Age-matched normotensive Wistar-Kyoto rats (WKY) and sham-operated Wistar rats served as respective controls. 3. Different methods were employed such as increasing the extracellular Ca2+ concentration, stimulation of calcium influx by means of the calcium entry promoter Bay K 8644, or altering the sodium-calcium exchange by means of the sodium ionophore monensin. 4. The inotropic responses induced by increasing the extracellular Ca2+ concentration or provoked by the calcium entry promoter Bay K 8644 proved more pronounced in hearts taken from SHR of 18 weeks old than in those from normotensive control rats, whereas the response to monensin was found to be the same in both types of hearts. In the hearts of ASR, however, the inotropic responses to Ca2+, Bay K 8644 and monensin were strongly impaired. 5. These data demonstrate that in functional experiments the sensitivity to Ca2+, which represents the main pathway in establishing a contraction, is strongly reduced in advanced cardiac hypertrophy.
Mertens
M J
MJ
Department of Pharmacotherapy, Faculty of Medicine, University of Amsterdam, Academic Medical Center, The Netherlands.
Pfaffendorf
M
M
Van Zwieten
P A
PA
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D006332:Cardiomegaly / Q000209:etiology / Q000378:metabolism* / Q000503:physiopathology; D003326:Coronary Circulation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications; D066298:In Vitro Techniques; D007477:Ions; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D012680:Sensitivity and Specificity
D007477:Ions; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D008985:Monensin; D002118:Calcium