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Long-term nitric oxide inhibition and chronotropic responses in rat isolated right atria
S R Riado1, A Zanesco, L A Barker
1Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, Campinas, Brazil.
Abstract:
The long-term administration of nitric oxide synthesis inhibitors induces arterial hypertension accompanied by left ventricular hypertrophy and myocardial ischemic lesions. Because the enhancement of sympathetic drive has been implicated in these phenomena, the current study was performed to determine the potency of beta-adrenoceptor agonists and muscarinic agonists on the spontaneous rate of isolated right atria from rats given long-term treatment with the nitric oxide inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME). Atrial lesions induced by long-term treatment with L-NAME were also evaluated. Long-term L-NAME treatment caused a time-dependent, significant (P<0.05) increase in tail-cuff pressure compared with control animals. Our results showed that the potency of isoproterenol, norepinephrine, carbachol, and pilocarpine in isolated right atria from rats given long-term treatment with L-NAME for 7, 15, 30, and 60 days was not affected as compared with control animals. Addition of L-NAME in vitro (100 microl/L) affected neither basal rate nor chronotropic response for isoproterenol and norepinephrine in rat heart. Stereological analysis of the right atria at 15 and 30 days revealed a significant increase on amount of fibrous tissues in L-NAME-treated groups (27+/-2.3% and 28+/-1.3% for 15 and 30 days, respectively; P<0.05) as compared with the control group (22+/-1.1%). Our results indicate that nitric oxide does not to interfere with beta-adrenoceptor-mediated and muscarinic receptor-mediated chronotropic responses.
Insights
Long-term inhibition of nitric oxide synthesis causes arterial hypertension and atrial fibrosis in rats. However, this treatment does not alter the heart
Area of Science:
- Cardiovascular Physiology
- Pharmacology
Background:
- Long-term administration of nitric oxide synthesis inhibitors, such as N(omega)-nitro-L-arginine methyl ester (L-NAME), is known to induce arterial hypertension, left ventricular hypertrophy, and myocardial ischemic lesions.
- Enhanced sympathetic drive has been implicated in these pathological phenomena.
Purpose of the Study:
- To investigate the impact of long-term nitric oxide inhibition on the chronotropic responses mediated by beta-adrenoceptors and muscarinic receptors in isolated rat atria.
- To evaluate atrial lesions, specifically fibrosis, resulting from chronic L-NAME treatment.
Main Methods:
- Rats were treated with L-NAME for varying durations (7, 15, 30, and 60 days).
- The potency of beta-adrenoceptor agonists (isoproterenol, norepinephrine) and muscarinic agonists (carbachol, pilocarpine) on the spontaneous rate of isolated right atria was assessed.
- In vitro addition of L-NAME was used to assess its direct effects on basal rate and chronotropic responses.
- Stereological analysis was employed to quantify fibrous tissue in atrial samples.
Main Results:
- Long-term L-NAME treatment significantly increased tail-cuff pressure in a time-dependent manner.
- The potency of isoproterenol, norepinephrine, carbachol, and pilocarpine on isolated rat atria was not affected by long-term L-NAME treatment.
- In vitro L-NAME did not alter basal heart rate or the chronotropic response to isoproterenol and norepinephrine.
- Stereological analysis revealed a significant increase in fibrous tissue in the atria of L-NAME-treated rats at 15 and 30 days.
Conclusions:
- Nitric oxide inhibition does not interfere with beta-adrenoceptor-mediated or muscarinic receptor-mediated chronotropic responses in the rat heart.
- Long-term nitric oxide inhibition leads to atrial fibrosis, independent of alterations in autonomic receptor-mediated heart rate regulation.