Purinergic P2X1 receptor, purinergic P2X7 receptor, and angiotensin II type 1 receptor interactions in the regulation of renal afferent arterioles in angiotensin II-dependent hypertension.

Abstract

In ANG II-dependent hypertension, ANG II activates ANG II type 1 receptors (AT1Rs), elevating blood pressure and increasing renal afferent arteriolar resistance (AAR). The increased arterial pressure augments interstitial ATP concentrations activating purinergic P2X receptors (P2XRs) also increasing AAR. Interestingly, P2X1R and P2X7R inhibition reduces AAR to the normal range, raising the conundrum regarding the apparent disappearance of AT1R influence. To evaluate the interactions between P2XRs and AT1Rs in mediating the increased AAR elicited by chronic ANG II infusions, experiments using the isolated blood perfused juxtamedullary nephron preparation allowed visualization of afferent arteriolar diameters (AAD). Normotensive and ANG II-infused hypertensive rats showed AAD responses to increases in renal perfusion pressure from 100 to 140 mmHg by decreasing AAD by 26 ± 10% and 19 ± 4%. Superfusion with the inhibitor P2X1Ri (NF4490; 1 μM) increased AAD. In normotensive kidneys, superfusion with ANG II (1 nM) decreased AAD by 16 ± 4% and decreased further by 19 ± 5% with an increase in renal perfusion pressure. Treatment with P2X1Ri increased AAD by 30 ± 6% to values higher than those at 100 mmHg plus ANG II. In hypertensive kidneys, the inhibitor AT1Ri (SML1394; 1 μM) increased AAD by 10 ± 7%. In contrast, treatment with P2X1Ri increased AAD by 21 ± 14%; combination with P2X1Ri plus P2X7Ri (A438079; 1 μM) increased AAD further by 25 ± 8%. The results indicate that P2X1R, P2X7R, and AT1R actions converge at receptor or postreceptor signaling pathways, but P2XR exerts a dominant influence abrogating the actions of AT1Rs on AAR in ANG II-dependent hypertension.

• Authors: Supaporn Kulthinee, Weijian Shao, Martha Franco, L Gabriel Navar
• Journal: American journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 318 Issue 6 Pg. F1400-F1408 (06 01 2020) ISSN: 1522-1466 [Electronic] United States
• PMID: 32308022 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Antihypertensive Agents
• P2rx7 protein, rat
• Purinergic P2X Receptor Antagonists
• Receptor, Angiotensin, Type 1
• Receptors, Purinergic P2X1
• Receptors, Purinergic P2X7
• Angiotensin II

Topics

• Angiotensin II
• Angiotensin II Type 1 Receptor Blockers (pharmacology)
• Animals
• Antihypertensive Agents (pharmacology)
• Arterioles (drug effects, metabolism, physiopathology)
• Blood Pressure (drug effects)
• Disease Models, Animal
• Hypertension (chemically induced, drug therapy, metabolism, physiopathology)
• Kidney (blood supply)
• Male
• Purinergic P2X Receptor Antagonists (pharmacology)
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1 (drug effects, metabolism)
• Receptors, Purinergic P2X1 (drug effects, metabolism)
• Receptors, Purinergic P2X7 (drug effects, metabolism)
• Signal Transduction