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

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 -adr enoceptor agonist isoprenaline in myocardial contractility, and whether thi s 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 ra ts (SHR). The contractile force of electrically-stimulated ventricular stri ps was measured by a force-displacement transducer. 3 Isoprenaline (from 10 nmol l(-1) to 10 mu mol l(-1)) induced a concentrat ion-dependent increase in cardiac contractility in strips from both rat str ains. 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 a nd 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]ox adiazolo[4,3]-quinoxalin-1-one (ODQ, 10 mu mol l(-1)), respective inhibitor s of NO synthase and guanylate cyclase, increased the response to isoprenal ine 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 incre ase in the response elicited by isoprenaline, which was similar to that obs erved with ODQ or L-NAME. 8-Br-cyclicGMP (8-Br-cGMP, 0.1 mmol l(-1)), a per meable and structural cGMP analogue, decreased the effect induced by isopre naline only in muscles from WKY rats. 6 These results suggest that the positive inotropic response to isoprenalin e in ventricular strips from WKY rats is negatively modulated by NO, and po sitively by superoxide anions in those from SHR. The lack of a modulatory r esponse to NO in ventricular strips from SHR is probably a result of an alt eration of mechanisms in NO-signalling pathway downstream of cGMP formation in SHR hearts.