Effect of acute nitric oxide synthase inhibition in the modulation of heart rate in rats.
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 micro M) 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.
Fellet
A L
AL
C tedra de Fisiolog a, Facultad de Farmacia y Bioqu mica, Universidad de Buenos Aires, Buenos Aires, Argentina. afellet@huemul.ffyb.uba.ar
Di Verniero
C
C
Arza
P
P
Tomat
A
A
Varela
A
A
Arranz
C
C
Balaszczuk
A M
AM
D000704:Analysis of Variance; D000818:Animals; D001340:Autonomic Nerve Block; D001341:Autonomic Nervous System / Q000187:drug effects*; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006325:Heart Atria; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley
D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester