Abstract: TH-OR81
Chemogenetic Activation of Pericytes Alters Systemic and Renal Hemodynamics
Session Information
- Mechanisms of Hypertension and Cardiorenal Disease: From the Vasculature to the Gut
November 02, 2023 | Location: Room 108, Pennsylvania Convention Center
Abstract Time: 04:30 PM - 04:39 PM
Category: Hypertension and CVD
- 1601 Hypertension and CVD: Basic
Authors
- Nelson, Jonathan W., Oregon Health & Science University, Portland, Oregon, United States
- Hagen, Matthew W., Oregon Health & Science University, Portland, Oregon, United States
- Gurley, Susan B., Oregon Health & Science University, Portland, Oregon, United States
Background
Pericytes are specialized cells that wrap around capillaries to provide structural and metabolic support. Pericytes have also been shown to respond to vasoactive compounds, such as angiotensin II, to constrict capillaries. However, the full functional consequence of pericyte activation on systemic and renal hemodynamics are poorly understood. To determine whether pericytes regulate systemic or renal hemodynamics we coupled a pericyte expressing cre line (Pdgfrb-creERT2) with the Gq-DREADD (Designer Receptor Exclusively Activated by Designer Drug) mouse to create Peri-DREADD mice which have pericyte-specific activation in the presence of a DREADD agonist.
Methods
Chemogenetic activation of pericytes was induced with intraperitoneal injection of the DREADD-specific agonist deschloroclozapine (DCZ) in Peri-DREADD mice and control littermates. Activation of pericytes was determined by measurement of cFos accumulation in pericyte nuclei by immunohistochemistry. Acute blood pressures were measured with a Millar catheter. Cortical and medullary perfusion was measured by contrast enhanced ultrasound. Sodium excretion was measured from urine collected in metabolic cages followed by electrolyte quantification with flame photometry.
Results
We find that Peri-DREADD mice express DREADD protein within pericytes which accumulate nuclear cFos after activation with DCZ. DCZ treatment of peri-DREADD mice acutely increases arterial pressure and decreases medullary and cortical perfusion. Sodium excretion increases following pericyte activation by DCZ.
Conclusion
Pericytes are capable of altering hemodynamics, particularly within the kidney where we observed decreases in cortical and medullary perfusion after chemogenetic activation concurrent with an increased natriuresis that correlates with an increase in systemic blood pressure.
Chemogenetic Activation of Peri-DREADD Mice Decreases Renal Perfusion.
Funding
- NIDDK Support