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Dissociation of coronary artery contractile hyperreactivity from hypertension
Wen Su1, Zhenheng Guo, Christian F Deschepper
1Department of Physiology, University of Kentucky College of Medicine, Lexington, Kentucky, USA.
Insights
Coronary artery hyperreactivity to 5-HT can occur independently of hypertension, suggesting it may contribute to coronary artery disease risk. G-protein signaling enhances this hyperreactivity in spontaneously hypertensive rats.
Area of Science:
- Cardiovascular Physiology
- Vascular Biology
- Hypertension Research
Background:
- Coronary artery contractile hyperreactivity and hypertension are linked to increased coronary artery disease (CAD).
- The relationship between coronary artery contractile hyperreactivity and hypertension remains unclear.
- This study investigated if coronary artery contractile hyperreactivity is independent of hypertension, potentially contributing to CAD etiology separately.
Purpose of the Study:
- To determine if coronary artery contractile hyperreactivity can be dissociated from hypertension.
- To investigate the role of G-protein-mediated signaling in coronary artery contractile hyperreactivity.
- To assess the contribution of coronary artery contractile hyperreactivity to coronary artery disease risk independent of hypertension.
Main Methods:
- Contractile responses to 5-hydroxytryptamine (5-HT) and guanosine triphosphate (GTP) were measured in rat coronary and mesenteric arteries.
- Experiments utilized intact and alpha-toxin-permeabilized arterial strips.
- Four rat strains were used: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), WKY-derived hypertensive rats (WKHT), and WKY-derived hyperactive rats (WKHA).
Main Results:
- Coronary artery contractile reactivity to 5-HT was significantly higher in hypertensive SHR compared to normotensive WKY rats.
- Contractile reactivity was intermediate in WKHA and WKHT rats, between SHR and WKY.
- GTP-induced Ca(2+) sensitization was greater in SHR, indicating increased G-protein signaling, but not significantly different among WKHT, WKHA, and WKY.
Conclusions:
- Coronary artery contractile hyperreactivity to 5-HT does not solely depend on blood pressure levels.
- Increased G-protein-mediated Ca(2+) sensitization contributes to coronary artery contractile hyperreactivity in spontaneously hypertensive rats.
- Coronary artery hyperreactivity may play a role in coronary artery disease independent of hypertension.
Background:
Both coronary artery contractile hyperreactivity and hypertension are associated with increased coronary artery disease. It is not known how coronary artery contractile hyperreactivity relates to hypertension. The current study tests the hypothesis that coronary artery contractile hyperreactivity can be dissociated from hypertension and therefore may contribute to the etiology of CAD independent of hypertension.
Methods:
The contractile responses to 5-hydroxytryptamine (5-HT) and guanosine triphosphate (GTP) were determined in intact (nonpermeabilized) and alpha-toxin-permeabilized coronary artery strips and small mesenteric artery strips isolated from four rat strains: spontaneously hypertensive rats (SHR), Wistar-Kyoto rats (WKY), WKY-derived hypertensive rats (WKHT), and WKY-derived hyperactive rats (WKHA).
Results:
The SHR and WKHT were hypertensive, whereas the WKY and WKHA subjects were normotensive. The coronary artery contractile reactivity to 5-HT was significantly higher in SHR when compared with WKY. The coronary artery contractile reactivity was of similar magnitude in WKHA and WKHT and was intermediate between that of SHR and WKY rats. GTP-induced Ca(2+) sensitization of contractions were significantly greater in SHR than in WKHT, WKHA, and WKY; in comparison, no significant difference was found among WKHT, WKHA, and WKY. In contrast to the findings in coronary arteries, there was no significant difference in 5-HT-induced contractions in small mesenteric artery strips isolated from SHR and WKY.
Conclusions:
Coronary artery contractile reactivity to 5-HT does not correlate entirely with blood pressure (BP) values. In addition, G-protein-mediated Ca(2+) sensitization of contraction was increased and contributed to the coronary artery contractile hyperreactivity in SHR.