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P2Y2 receptor activation decreases blood pressure and increases renal Na+ excretion
- Publication Year :
- 2011
- Publisher :
- American Physiological Society, 2011.
-
Abstract
- ATP and UTP are endogenous agonists of P2Y2/4receptors. To define the in vivo effects of P2Y2receptor activation on blood pressure and urinary excretion, we compared the response to INS45973, a P2Y2/4receptor agonist and UTP analog, in wild-type (WT) and P2Y2receptor knockout (P2Y2−/−) mice. INS45973 was administered intravenously as a bolus injection or continuous infusion to determine effects on blood pressure and renal function, respectively. Within seconds, bolus application of INS45973 (0.1 to 3 mg/kg body wt) dose-dependently decreased blood pressure in WT (maximum response −35 ± 2 mmHg) and to a similar extent in endothelial nitric oxide synthase knockout mice. By contrast, blood pressure increased in P2Y2−/− (maximum response +18 ± 1 mmHg) but returned to basal levels within 60 s. Continuous infusion of INS45973 (25 to 750 μg·min−1·kg−1body wt) dose-dependently increased urinary excretion of Na+in WT (maximum response +46 ± 15%) but reduced Na+excretion in P2Y2−/− (maximum responses of −45 ± 15%) mice. In renal clearance experiments, INS45973 did not affect glomerular filtration rate but lowered blood pressure and increased fractional excretion of fluid, Na+, and K+in WT relative to P2Y2−/− mice. The blood pressure responses to INS45973 are consistent with P2Y2receptor-mediated NO-independent vasodilation and implicate responses to endothelium-derived hyperpolarizing factor, and P2Y2receptor-independent vasoconstriction, probably via activation of P2Y4receptors on smooth muscle. Systemic activation of P2Y2receptors thus lowers blood pressure and inhibits renal Na+reabsorption, effects suggesting the potential utility of P2Y2agonism in the treatment of hypertension.
- Subjects :
- medicine.medical_specialty
Nitric Oxide Synthase Type III
Physiology
Vasodilation
Blood Pressure
Uridine Triphosphate
Kidney
Excretion
Receptors, Purinergic P2Y2
Mice
Physiology (medical)
Internal medicine
medicine
Animals
Receptor
Mice, Knockout
Reabsorption
Chemistry
Research
Inosine
Endocrinology
Blood pressure
medicine.anatomical_structure
Gene Expression Regulation
Purinergic Agonists
Decreased blood pressure
medicine.symptom
Vasoconstriction
Glomerular Filtration Rate
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Accession number :
- edsair.doi.dedup.....e30e233fa9309b4e2da0234f2e90c510