Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats

Abstract

Acute nitric oxide synthase inhibition with N G -nitro-L-arginine methyl ester (L-NAME) on chronotropic and pressor responses was studied in anesthetized intact rats and rats submitted to partial and complete autonomic blockade. Blood pressure and heart rate were monitored intra-arterially. Intravenous L-NAME injection (7.5 mg/kg) elicited the same hypertensive response in intact rats and in rats with partial (ganglionic and parasympathetic blockade) and complete autonomic blockade (38 ± 3, 55 ± 6, 54 ± 5, 45 ± 5 mmHg, respectively; N = 9, P = NS). L-NAME-induced bradycardia at the time when blood pressure reached the peak plateau was similar in intact rats and in rats with partial autonomic blockade (43 ± 8, 38 ± 5, 46 ± 6 bpm, respectively; N = 9, P = NS). Rats with combined autonomic blockade showed a tachycardic response to L-NAME (10 ± 3 bpm, P<0.05 vs intact animals, N = 9). Increasing doses of L-NAME (5.0, 7.5 and 10 mg/kg, N = 9) caused a similar increase in blood pressure (45 ± 5, 38 ± 3, 44 ± 9 mmHg, respectively; P = NS) and heart rate (31 ± 4, 34 ± 3, 35 ± 4 bpm, respectively; P = NS). Addition of L-NAME (500 µM) to isolated atria from rats killed by cervical dislocation and rats previously subjected to complete autonomic blockade did not affect spontaneous beating or contractile strength (N = 9). In vivo results showed that L-NAME promoted a tachycardic response in rats with complete autonomic blockade, whereas the in vitro experiments showed no effect on intrinsic heart rate, suggesting that humoral mechanisms may be involved in the L-NAME-induced cardiac response.

Nitric oxide and cardiac function

“…In fact, it has been observed that in the rat with autonomic-blocked N G -nitro-Larginine methyl-ester (L-NAME) administration induces tachycardia, along with an increase in blood pressure. These effects are partially prevented by thyroidectomy and are not affected by adrenalectomy (Fellet et al, 2003(Fellet et al, , 2004. The tachycardic effects of NO inhibition in this rat model are in contrast to those observed by Ward and Angus (1993) in the rabbit.…”

Exogenous intravascular nitric oxide enhances ventricular function after hemodilution with plasma expander

“…The role of NO in the regulation of cardiac function and circulatory system has been remarkably studied in both normal and pathological conditions (Bolli, et al 1998,Fellet, et al 2003,Kojda, et al 1997,Colley and Sivarajan 1984,Crystal, et al 1988). The principal reported effect of NO on cardiac function describes bimodal effects on inotropy with positive inotropic effects at reduced NO availability, and negative inotropic effects at increased NO availability (Kojda, et al 1997,Preckel, et al 1997,Brady, et al 1993).…”

Nitric oxide and thyroid gland: modulation of cardiovascular function in autonomic‐blocked anaesthetized rats

“…The addition of l‐ NAME in isolated atria, in an equivalent dose used in in vivo experiments, did not affect either chronotropic or inotropic effects. Thus, the l‐ NAME‐induced tachycardia, observed in vivo , might not be due to a direct action of the inhibitor on the pacemaker (Fellet et al 2003). Alterations in thyroid and adrenal status, in secretions of vasoactive substances (Nagayama et al 1998; Dillmann, 2002; Lee et al 2002), as well as physical factors such as shear stress might be involved in this positive chronotropic response (Iadecola et al 1994).…”