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Maternal high salt diet altered Adenosine-mediated vasodilatation via PKA/BK channel pathway in offspring rats
Jue Wu1, Na Li1, Yanping Liu1
1Institute for Fetology, First Hospital of Soochow University, Suzhou, China.
Insights
Prenatal high salt diets impair coronary artery function in offspring. This is linked to reduced adenosine-induced vasodilation via the cAMP/protein kinase A (PKA)/BK channel pathway.
Area of Science:
- Cardiovascular Physiology
- Developmental Biology
- Pharmacology
Background:
- High salt (HS) diets are associated with cardiovascular diseases.
- Prenatal exposure to HS diets may increase offspring's risk of coronary artery disease.
- The adenosine signaling pathway plays a role in coronary artery function.
Purpose of the Study:
- To investigate the effect of prenatal HS diet on adenosine-induced vasodilation in offspring coronary arteries.
- To determine the involvement of the protein kinase A (PKA) pathway in mediating these effects.
- To explore the role of potassium (K+) channels, specifically the large-conductance Ca2+-activated K+ (BK) channel.
Main Methods:
- Gestation Sprague-Dawley rats were fed either an 8% salt (HS) or 0.3% salt (control) diet.
- Coronary arteries from male adult offspring were analyzed for K+ channel and adenosine signaling pathway components.
- Functional assays included measuring vasodilation responses to adenosine and forskolin, with and without PKA or BK channel inhibitors.
Main Results:
- Adenosine-mediated vasodilation was reduced in offspring exposed to prenatal HS diet.
- No significant difference in A2A receptor gene expression was observed between groups.
- Inhibition of PKA or BK channels differentially affected vasodilation in HS and control groups, indicating pathway alterations.
- BK channel currents and protein levels of BK β1 and PKA C-subunits were reduced in HS offspring.
Conclusions:
- Prenatal HS diet significantly alters adenosine-mediated vasodilation in adult offspring coronary arteries.
- The observed changes are associated with a downregulation of the cAMP/PKA/BK channel signaling pathway.
- These findings highlight a potential mechanism linking maternal diet to offspring cardiovascular health.
Scope:
High salt (HS) diets are related to cardiovascular diseases, and prenatal HS was suggested to increase risks of coronary artery diseases in the offspring. This study tested the hypothesis that prenatal HS may influence Adenosine-induced vasodilatation via protein kinase A (PKA) pathway in coronary arteries.
Methods And Results:
Sprague-Dawley rats were fed with 8% salt diet for gestation, the control was fed with 0.3% salt diet. Coronary arteries from male adult offspring were tested for K+ channels and Adenosine signal pathways. Adenosine-mediated vasodilatation was reduced in coronary arteries in HS. There was no difference in gene expression of A2A receptors between the two groups. After pretreatment with PKA inhibitor, vasodilatation to Adenosine was decreased to a smaller extent in HS than that in control. Forskolin (activator of adenylate cyclase)-mediated vasodilatation was decreased in HS. Iberiotoxin (large-conductance Ca2+ -activated K+ channel [BK channel] inhibitor) attenuated Forskolin-induced vasodilatation in control, not in HS group. Currents of BK channels decreased in coronary artery smooth muscle cells, and PKA-modulated BK channel functions were declined. Protein levels of BK β1 and PKA C-subunits in coronary arteries of HS offspring were reduced.
Conclusions:
Prenatal HS diets altered Adenosine-mediated coronary artery vasodilatation in the offspring, which was linked to downregulation of cAMP/PKA/BK channel pathway.
