What is the clinical evidence from this study?

Study design: Other. Population: Hypertension (n=110). Intervention: L-NAME (NG-nitro-L-arginine methyl ester) vs. Solvent (water). Primary outcome: Aortic cGMP content (p=<0.0001).

What question did this study set out to answer?

This research aims to explore how chronic inhibition of nitric oxide synthase affects aortic cGMP levels and blood pressure in rats.

August 1, 1992Journal of Clinical InvestigationOpen Access

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

Q: What are the key findings of this study?

Chronic blockade of nitric oxide synthase with L-NAME induced a dose-dependent increase in blood pressure and a 10-fold decrease in aortic cGMP in rats.

Q: What question did this study set out to answer?

This research aims to explore how chronic inhibition of nitric oxide synthase affects aortic cGMP levels and blood pressure in rats.

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Key result

Chronic blockade of nitric oxide synthase with L-NAME induced a dose-dependent increase in blood pressure and a 10-fold decrease in aortic cGMP in rats.

Population

Wistar rats (n = 10 per group, 7 groups)

Comparison

NG-nitro-L-arginine methyl ester at doses of 1… vs 0 mg/kg.d L-NAME (control)

Design

Preclinical

Follow-up

4 weeks

Authors

JAJean‐François ArnalUniversité Toulouse III - Paul Sabatier LWL WarinInserm JMJean‐Baptiste MichelUniversité Claude Bernard Lyon 1

Discussion

Member takes

Implication

Supports NO-cGMP pathway in BP control; hypothesis-generating for human hypertension and should not yet change practice.

Key Points

This research aims to explore how chronic inhibition of nitric oxide synthase affects aortic cGMP levels and blood pressure in rats.
Wistar rats (n = 10 per group) received varying doses of L-NAME for 4 weeks.
Blood pressure and cGMP levels were measured and analyzed for correlations with endogenous ANF.
The study assessed the effects of intravenous L-arginine and exogenous ANF on blood pressure and cGMP levels.
Chronic L-NAME led to a dose-dependent increase in blood pressure and a 10-fold decrease in aortic cGMP levels.
Plasma cGMP levels did not significantly change but were correlated with plasma ANF levels (r = 0.51, P < 0.0001).
Exogenous ANF and sodium nitroprusside significantly increased aortic cGMP and intravenous L-arginine reversed arterial pressure increases.

Structured PICO

Population

110 young male Wistar rats weighing 120-130 g, treated with varying doses of L-NAME for 4 weeks to evaluate the determinants of aortic cGMP in induced hypertension.

Intervention

NG-nitro-L-arginine methyl ester (L-NAME) at doses of 1, 5, 10, 20, 50, and 100 mg/kg.d by gavage twice a day for 4 weeks

Comparator

0 mg/kg.d L-NAME (control)

Outcome

Blood pressure and plasma and aortic cGMP levelssurrogate

Main Result

Absolute Event Rate: 270% vs 2433%

p-value: p=<0.0001

Chronic blockade of NO synthase with L-NAME in rats induces hypertension and decreases aortic cGMP, demonstrating that basal aortic cGMP depends mainly on NO synthase.

Limitations

The discrepancy between high blood pressure and the absence of cardiac hypertrophy requires further investigation.
Cellular heterogeneity of the organs makes it difficult to assess the in vivo status of the second messengers.

Cite This Study

Arnal et al. (1992) studied Hypertension (n=110). L-NAME (NG-nitro-L-arginine methyl ester) vs. Solvent (water) was evaluated on Aortic cGMP content (p=<0.0001). Chronic blockade of nitric oxide synthase with L-NAME induced a dose-dependent increase in blood pressure and a 10-fold decrease in aortic cGMP in rats.

synapsesocial.com/papers/6a6eebea35aa2c282ce0702e https://doi.org/10.1172/jci115906

Topics

Hypertension management

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Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Topics

Determinants of aortic cyclic guanosine monophosphate in hypertension induced by chronic inhibition of nitric oxide synthase.

Discussion

Member takes

Implication

Key Points

Structured PICO

Main Result

Limitations

Cite This Study

Also Consider

Topics

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