L-NAME hypertension alters endothelial and smooth muscle function in rat aorta. Prevention by trandolapril and verapamil
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Abstract:
Nitric oxide is an important regulator of vascular function and blood pressure. Chronic administration of nitric oxide inhibitors provides a new model of hypertension with pronounced target organ damage. We investigated the effects of oral treatment with N omega-nitro-L-arginine methyl ester (L-NAME) for 6 weeks on vascular reactivity of the aorta in Wistar-Kyoto rats. Certain rats received verapamil or trandolapril in addition to L-NAME. Systolic blood pressure increased in the L-NAME group (by approximately or equal to 80 mm Hg systolic) but not in controls or rats treated with verapamil or trandolapril. Isometric tension changes of aortic rings were recorded. Endothelium-dependent relaxations to acetylcholine were reduced in the L-NAME group (58 +/- 6% versus 104 +/- 1% in placebo, P < .05) but were normalized by treatment with verapamil or trandolapril. In contrast, endothelium-independent relaxations to sodium nitroprusside were not significantly reduced in L-NAME hypertension but were slightly enhanced by trandolapril therapy (P < .05) in the L-NAME group only. In quiescent rings, acetylcholine caused endothelium-dependent contractions in particular after in vitro incubation with L-NAME. These contractions tended to be enhanced in L-NAME hypertension (23 +/- 4% versus 14 +/- 3% in the placebo group; P = NS) and were significantly reduced after treatment with verapamil or trandolapril (P < .05). Concentrations to norepinephrine and angiotensin I and II were unaffected by L-NAME hypertension, whereas those to endothelin-1 were reduced (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
Insights
Chronic nitric oxide inhibition causes hypertension and vascular dysfunction in rats. Verapamil and trandolapril treatments normalized blood pressure and improved aortic ring relaxation, highlighting their therapeutic potential.
Area of Science:
- Cardiovascular Physiology
- Pharmacology
- Hypertension Research
Background:
- Nitric oxide (NO) is crucial for regulating vascular function and blood pressure.
- Chronic inhibition of NO synthesis leads to hypertension and target organ damage.
- N omega-nitro-L-arginine methyl ester (L-NAME) is a tool for modeling hypertension.
Purpose of the Study:
- To investigate the effects of L-NAME-induced hypertension on aortic vascular reactivity in rats.
- To evaluate the efficacy of verapamil and trandolapril in mitigating L-NAME-induced vascular dysfunction.
Main Methods:
- Oral administration of L-NAME for 6 weeks to induce hypertension in Wistar-Kyoto rats.
- Assessment of systolic blood pressure and isometric tension changes in isolated aortic rings.
- Measurement of endothelium-dependent and -independent relaxations and contractions.
Main Results:
- L-NAME significantly increased systolic blood pressure, an effect blunted by verapamil and trandolapril.
- Endothelium-dependent relaxations to acetylcholine were impaired by L-NAME but restored by verapamil/trandolapril.
- L-NAME induced endothelium-dependent contractions, which were reduced by verapamil and trandolapril.
Conclusions:
- L-NAME effectively models hypertension with significant vascular alterations.
- Verapamil and trandolapril demonstrate protective effects against L-NAME-induced hypertension and vascular dysfunction.
- These findings support the role of NO in maintaining vascular homeostasis and suggest therapeutic benefits of calcium channel blockers and ACE inhibitors in hypertension.