Desensitization of β-Adrenoceptor-Mediated Functional Responses of Guinea Pig Atria by In Vitro Incubation with Isoprenaline

Herepath, Michael L.; Broadley, Kenneth J.

doi:10.1097/00005344-199002000-00013

Cited by 12 publications

(6 citation statements)

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“…The values of different points of the curve in the presence of an antagonist were then corrected for time‐dependent changes in sensitivity occurring during the experiment by application of correction factors derived from the appropriate control experiment. Correction factors were obtained by expressing the mean total tension for each concentration on the second curve of control experiments as a fraction of the total value for the corresponding concentration on the first curve ( Herepath & Broadley 1990).…”

Section: Methodsmentioning

confidence: 99%

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats

Manso¹,

Encabo²,

Ferrer

et al. 1999

Journal of Autonomic Pharmacology

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The aim of the present study was to assess the alterations in cardiac Ca2+ homeostasis induced by hypertension using electrically paced right ventricular strips from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). 2 Basal contractile force was higher in SHR than in WKY. Similarly, the beta-adrenoceptor agonist isoprenaline (10 nM-10 microM) induced a concentration-dependent positive inotropic effect that was higher in SHR than in WKY, which was in turn inhibited by the beta-adrenoceptor antagonist propranolol (1 microM) in both strains. 3 Preincubation of strips with the L-type Ca2+ channel blockers, nifedipine (1 microM) or verapamil (10 microM), markedly inhibited the isoprenaline response, the inhibition being higher in SHR than in WKY. However, this inhibition was minor by the T-type Ca2+ channel blocker mibefradil (10 microM). 4 Bay K 8644 (10 nM-10 microM), a L-type Ca2+ channel activator induced a concentration-dependent positive inotropic effect, that was greater in SHR than WKY. 5 Nifedipine and verapamil (both 0.1 nM-10 microM) inhibited in a concentration-dependent way the inotropic effect induced by 0.3 microM isoprenaline or 1 microM Bay K 8644. The inhibition was higher in SHR than in WKY. Mibefradil (0.1 nM-10 microM) only clearly inhibited the isoprenaline and Bay K 8644 inotropic effects at 10 microM in both strains. 6 The inhibitor of the sarcoplasmic reticulum Ca2+ release, ryanodine (10 nM-10 microM), was a more effective depressor of isoprenaline-induced response in SHR than in WKY. 7 These results suggest that cardiac Ca2+ homeostasis in SHR ventricular strips is altered compared with those of WKY, showing an increased Ca2+ entry through L-type Ca2+ channels and release from sarcoplasmic reticulum; the participation of T-type Ca2+ channels are irrelevant in this tissue.

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Section: Methodsmentioning

confidence: 99%

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats

Manso¹,

Encabo²,

Ferrer

et al. 1999

Journal of Autonomic Pharmacology

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“…In the sustained presence of high agonist concentrations, many receptor types undergo desensitization. The effects are qualitatively similar to those of receptor alkylation, i.e., the concentration-response curves are dextrally shifted and the maxima, upon depletion of the spare receptors, are depressed (Eglen et al, 1987;Herepath & Broadley, 1990). However, unless the desensitization process is homologous, i.e.…”

Section: Introductionmentioning

confidence: 91%

“…The procedure employed was similar to that described above except that isoprenaline (3.2-560 nM) was substituted for BAAM, and left in contact with the preparations for 120 min. This period was chosen since Herepath & Broadley (1990) have shown that exposure greater than 4 h resulted in irreversible desensitization (i.e. down regulation).…”

Section: Receptor Desensitization Studiesmentioning

confidence: 99%

“…Positive inotropic responses to fladrenoceptor agonists in rat isolated left atria were used as a model to test this approach for several reasons. Firstly, rat atria have been well characterized in terms of the receptor populations by both radioligand and functional binding techniques (Juberg et al, 1985;Montgomery et al, 1988a;Herepath & Broadley, 1990). Secondly, short term fi-adrenoceptor desensitization in cardiac tissue is generally homologous (see Harden, 1983 for review).…”

Section: Introductionmentioning

confidence: 99%

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Desensitization and functional antagonism by β‐adrenoceptor and muscarinic receptor agonists, respectively: a comparison with receptor alkylation for calculation of apparent agonist affinity

Eglen¹,

Montgomery²,

Whiting³

1991

British J Pharmacology

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“…The values of different points of the curve in the presence of the above mentioned inhibitors were then corrected for time-dependent changes in sensitivity occurring during the experiment by application of correction factors derived from the appropriate control experiment. Correction factors were obtained by expressing the mean total tension for each concentration on the second curve of control experiments as a fraction of the total value for the corresponding concentration on the first curve (Herepath & Broadley, 1990).…”

Section: Analysis Of Datamentioning

confidence: 99%

Different sensitivity of isoprenaline‐induced responses in ventricular muscle to sodium nitroprusside in normotensive and spontaneously hypertensive rats 1

Manso

Encabo²,

Redondo³

et al. 2000

J. Autonom. Pharmacol.

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1. The aim of the present work was to study the possible modulatory role of nitric oxide (NO) on the positive inotropic effect induced by the beta-adrenoceptor agonist isoprenaline in myocardial contractility, and whether this modulation is altered by hypertension. 2. The study was performed using right ventricular strips from the hearts of 6-month-old male Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). The contractile force of electrically-stimulated ventricular strips was measured by a force-displacement transducer. 3. Isoprenaline (from 10 nmol l(-1) to 10 micromol l(-1)) induced a concentration-dependent increase in cardiac contractility in strips from both rat strains. This positive inotropic effect to isoprenaline was reduced by the NO donor sodium nitroprusside (SNP, 0.1 mmol l(-1)) in muscles from WKY rats and slightly increased in those from SHR. The SNP-induced increase in strips from SHR was abolished by superoxide dismutase (100 U ml(-1)). 4. N(G)-nitro-arginine-methyl ester (L-NAME, 0.1 mmol l(-1)) and 1H-[1,2,4]oxadiazolo[4,3]-quinoxalin-1-one (ODQ, 10 micromol l(-1)), respective inhibitors of NO synthase and guanylate cyclase, increased the response to isoprenaline in muscles from WKY rats, whereas it was unaltered in strips from SHR. 5. In strips from WKY rats, the combination of ODQ and SNP produced an increase in the response elicited by isoprenaline, which was similar to that observed with ODQ or L-NAME. 8-Br-cyclicGMP (8-Br-cGMP, 0.1 mmol l(-1)), a permeable and structural cGMP analogue, decreased the effect induced by isoprenaline only in muscles from WKY rats. 6. These results suggest that the positive inotropic response to isoprenaline in ventricular strips from WKY rats is negatively modulated by NO, and positively by superoxide anions in those from SHR. The lack of a modulatory response to NO in ventricular strips from SHR is probably a result of an alteration of mechanisms in NO-signalling pathway downstream of cGMP formation in SHR hearts.

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Desensitization of β-Adrenoceptor-Mediated Functional Responses of Guinea Pig Atria by In Vitro Incubation with Isoprenaline

Cited by 12 publications

References 0 publications

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats

Changes of cardiac calcium homeostasis in spontaneously hypertensive rats

Desensitization and functional antagonism by β‐adrenoceptor and muscarinic receptor agonists, respectively: a comparison with receptor alkylation for calculation of apparent agonist affinity

Different sensitivity of isoprenaline‐induced responses in ventricular muscle to sodium nitroprusside in normotensive and spontaneously hypertensive rats 1

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