monensin and Hypertension

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.

Topics: 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; Animals; Blood Pressure; Calcium; Cardiomegaly; Coronary Circulation; Extracellular Space; Heart; Heart Rate; Hypertension; In Vitro Techniques; Ions; Male; Monensin; Myocardial Contraction; Myocardium; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Rats, Wistar; Sensitivity and Specificity

We have compared the effect of Na+ and K+ on the serotonin secretion induced by thrombin in platelets from spontaneously hypertensive rats (SHR) and age-matched control animals (WKY). Decrease in external Na+ concentration did not modify the secretory response of either species of platelets; furthermore addition of veratridine and amiloride had no effect. Elevation of external K+ concentration stimulated the thrombin-induced 5-HT secretion, even in the absence of external Ca2+, in both species of platelet, and addition of monensin induced a selective release of serotonin without modifying the response to subsequent addition of thrombin. Platelet secretion therefore appears not to be identical to neuronal secretion and the observed difference between SHR and WKY platelets does not seem to depend upon alteration in Na+ and K+ cellular metabolism.

Topics: Amiloride; Animals; Blood Platelets; Hypertension; Monensin; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Rats, Inbred WKY; Serotonin; Sodium; Stimulation, Chemical; Thrombin; Veratridine

This study characterizes isometric force development in response to ouabain and K+-free solution in isolated aortic strips from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats. SHR aortas were more sensitive to ouabain than those from WKY (threshold: SHR, 3.1 X 10(-5) M; WKY, 25.6 X 10(-5) M), and force development in response to 10(-3) M ouabain was greater in SHR (SHR, 586 +/- 51 mg; WKY, 245 +/- 24 mg). Monensin, a Na+ ionophore, potentiated contractile responses to ouabain, whereas amiloride, a Na+ channel blocker, and low Na+ solutions depressed contractile responses to ouabain. Contractile responses of SHR aortic strips to K+-free solution were faster than those of WKY aortic strips [time to half-maximal response (t1/2): SHR, 24 +/- 5 min; WKY, 47 +/- 4 min]. Maximal force development by aortic strips from SHR in response to K+-free solution was not different from that of WKY aortic strips (SHR, 808 +/- 34 mg; WKY, 750 +/- 37 mg). Monensin (10(-5) M) increased the rate of force development to K+-free solution to a greater extent in WKY aortic strips than in those from SHR (t1/2: SHR, 3 +/- 1 min; WKY, 4 +/- 2 min). Amiloride and low Na+ solution depressed contractile responses to K+-free solution in both SHR and WKY aortic strips. These observations demonstrate that SHR aortas are more responsive to ouabain and K+-free solution compared with WKY aortas. Contractile responses to ouabain and K+-free solution were sensitive to experimental interventions that alter transmembrane Na+ movements.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Amiloride; Animals; Aorta; Dose-Response Relationship, Drug; Hypertension; In Vitro Techniques; Male; Membrane Potentials; Monensin; Muscle Contraction; Muscle, Smooth, Vascular; Ouabain; Potassium; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Sodium