Abstract
There is growing evidence that sphingosine 1-phosphate (S1P) plays an important role in regulating the development, morphology, and function of the cardiovascular system. There is little data, however, regarding the relative contribution of endogenous S1P and its cognate receptors (referred to as S1P1-5) to cardiovascular homeostasis. We used S1P2 receptor knockout mice (S1P2-/-) to evaluate the role of S1P2 in heart and vascular function. There were no significant differences in blood pressure between wild-type and S1P2 -/- mice, measured in awake mice. Cardiac function, evaluated in situ by using a Millar catheter, was also not different in S1P2 -/- mice under baseline or stimulated conditions. In vivo analysis of vascular function by flowmetry revealed decreases in mesenteric and renal resistance in S1P2-/- mice, especially during vasoconstriction with phenylephrine. In intact aortic rings, the concentration-force relations for both KCl and phenylephrine were right shifted in S1P2-/- mice, whereas the maximal isometric forces were not different. By contrast, in deendothelialized rings the concentration-force relations were not different but the maximal force was significantly greater in S1P2-/- aorta. Histologically, there were no apparent differences in vascular morphology. These data suggest that the S1P2 receptor plays an important role in the function of the vasculature and is an important mediator of normal hemodynamics. This is mediated, at least in part, through an effect on the endothelium, but direct effects on vascular smooth muscle cannot be ruled out and require further investigation.
| Original language | English (US) |
|---|---|
| Journal | American Journal of Physiology - Regulatory Integrative and Comparative Physiology |
| Volume | 292 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 1 2007 |
| Externally published | Yes |
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Keywords
- Blood flow
- Endothelium
- Lysosphingolipids
- Myocardial contractility
- Vascular smooth muscle
ASJC Scopus subject areas
- Physiology
Cite this
Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice. / Lorenz, John N.; Arend, Lois J.; Robitz, Rachel A; Paul, Richard J.; MacLennan, A. John.
In: American Journal of Physiology - Regulatory Integrative and Comparative Physiology, Vol. 292, No. 1, 01.01.2007.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Vascular dysfunction in S1P2 sphingosine 1-phosphate receptor knockout mice
AU - Lorenz, John N.
AU - Arend, Lois J.
AU - Robitz, Rachel A
AU - Paul, Richard J.
AU - MacLennan, A. John
PY - 2007/1/1
Y1 - 2007/1/1
N2 - There is growing evidence that sphingosine 1-phosphate (S1P) plays an important role in regulating the development, morphology, and function of the cardiovascular system. There is little data, however, regarding the relative contribution of endogenous S1P and its cognate receptors (referred to as S1P1-5) to cardiovascular homeostasis. We used S1P2 receptor knockout mice (S1P2-/-) to evaluate the role of S1P2 in heart and vascular function. There were no significant differences in blood pressure between wild-type and S1P2 -/- mice, measured in awake mice. Cardiac function, evaluated in situ by using a Millar catheter, was also not different in S1P2 -/- mice under baseline or stimulated conditions. In vivo analysis of vascular function by flowmetry revealed decreases in mesenteric and renal resistance in S1P2-/- mice, especially during vasoconstriction with phenylephrine. In intact aortic rings, the concentration-force relations for both KCl and phenylephrine were right shifted in S1P2-/- mice, whereas the maximal isometric forces were not different. By contrast, in deendothelialized rings the concentration-force relations were not different but the maximal force was significantly greater in S1P2-/- aorta. Histologically, there were no apparent differences in vascular morphology. These data suggest that the S1P2 receptor plays an important role in the function of the vasculature and is an important mediator of normal hemodynamics. This is mediated, at least in part, through an effect on the endothelium, but direct effects on vascular smooth muscle cannot be ruled out and require further investigation.
AB - There is growing evidence that sphingosine 1-phosphate (S1P) plays an important role in regulating the development, morphology, and function of the cardiovascular system. There is little data, however, regarding the relative contribution of endogenous S1P and its cognate receptors (referred to as S1P1-5) to cardiovascular homeostasis. We used S1P2 receptor knockout mice (S1P2-/-) to evaluate the role of S1P2 in heart and vascular function. There were no significant differences in blood pressure between wild-type and S1P2 -/- mice, measured in awake mice. Cardiac function, evaluated in situ by using a Millar catheter, was also not different in S1P2 -/- mice under baseline or stimulated conditions. In vivo analysis of vascular function by flowmetry revealed decreases in mesenteric and renal resistance in S1P2-/- mice, especially during vasoconstriction with phenylephrine. In intact aortic rings, the concentration-force relations for both KCl and phenylephrine were right shifted in S1P2-/- mice, whereas the maximal isometric forces were not different. By contrast, in deendothelialized rings the concentration-force relations were not different but the maximal force was significantly greater in S1P2-/- aorta. Histologically, there were no apparent differences in vascular morphology. These data suggest that the S1P2 receptor plays an important role in the function of the vasculature and is an important mediator of normal hemodynamics. This is mediated, at least in part, through an effect on the endothelium, but direct effects on vascular smooth muscle cannot be ruled out and require further investigation.
KW - Blood flow
KW - Endothelium
KW - Lysosphingolipids
KW - Myocardial contractility
KW - Vascular smooth muscle
UR - http://www.scopus.com/inward/record.url?scp=33846135087&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846135087&partnerID=8YFLogxK
U2 - 10.1152/ajpregu.00085.2006
DO - 10.1152/ajpregu.00085.2006
M3 - Article
C2 - 16990495
AN - SCOPUS:33846135087
VL - 292
JO - American Journal of Physiology
JF - American Journal of Physiology
SN - 0363-6119
IS - 1
ER -