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Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats.
Am J Physiol. 1999 05; 276(5):F767-76.AJ

Abstract

Profound vasodilation of the kidneys and other nonreproductive organs transpires during early pregnancy. Because nitric oxide (NO) was found to mediate renal vasodilation and hyperfiltration in conscious pregnant rats, and endogenous endothelin (ET) was suggested to be vasodilatory in the renal circulation of nonpregnant rats, we tested whether endothelin mediates the NO-dependent changes in the renal circulation during pregnancy. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in conscious pregnant and virgin rats before and during infusion of 30 micrograms/min RES-701-1 (a selective ETB receptor subtype antagonist). Baseline GFR and ERPF were significantly increased by 35% in gravid rats relative to virgin controls. During infusion of RES-701-1, the pregnant rats responded more robustly, showing a greater decline in both GFR and ERPF such that renal function converged in the two groups of rats. ERPF also converged in pregnant and virgin rats during infusion of SB-209760, a nonselective ETA/B receptor subtype antagonist. Combined infusion of Nomega-nitro-L-arginine methyl ester [L-NAME, an NO synthase (NOS) inhibitor] and RES-701-1 reduced GFR and ERPF to levels comparable to those reached with either agent given alone, suggesting inhibition of a common vasodilatory pathway. RES-701-1 and SB-209670 significantly lowered the cGMP content of small renal arteries from gravid and virgin rats in vitro, strengthening the link between the renal endothelial ETB receptor subtype and NO. Importantly, we showed that RES-701-1 is not a direct inhibitor of NOS. We conclude that endothelin mediates the NO-dependent changes in the renal circulation of conscious rats during pregnancy.

Authors+Show Affiliations

Departments of Obstetrics, Gynecology and Reproductive Sciences, and of Cell Biology and Physiology, University of Pittsburgh, Magee-Womens Research Institute, Pittsburgh, Pennsylvania 15213, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

10330059

Citation

Conrad, K P., et al. "Endothelin Mediates Renal Vasodilation and Hyperfiltration During Pregnancy in Chronically Instrumented Conscious Rats." The American Journal of Physiology, vol. 276, no. 5, 1999, pp. F767-76.
Conrad KP, Gandley RE, Ogawa T, et al. Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats. Am J Physiol. 1999;276(5):F767-76.
Conrad, K. P., Gandley, R. E., Ogawa, T., Nakanishi, S., & Danielson, L. A. (1999). Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats. The American Journal of Physiology, 276(5), F767-76. https://doi.org/10.1152/ajprenal.1999.276.5.F767
Conrad KP, et al. Endothelin Mediates Renal Vasodilation and Hyperfiltration During Pregnancy in Chronically Instrumented Conscious Rats. Am J Physiol. 1999;276(5):F767-76. PubMed PMID: 10330059.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Endothelin mediates renal vasodilation and hyperfiltration during pregnancy in chronically instrumented conscious rats. AU - Conrad,K P, AU - Gandley,R E, AU - Ogawa,T, AU - Nakanishi,S, AU - Danielson,L A, PY - 1999/5/18/pubmed PY - 1999/5/18/medline PY - 1999/5/18/entrez SP - F767 EP - 76 JF - The American journal of physiology JO - Am J Physiol VL - 276 IS - 5 N2 - Profound vasodilation of the kidneys and other nonreproductive organs transpires during early pregnancy. Because nitric oxide (NO) was found to mediate renal vasodilation and hyperfiltration in conscious pregnant rats, and endogenous endothelin (ET) was suggested to be vasodilatory in the renal circulation of nonpregnant rats, we tested whether endothelin mediates the NO-dependent changes in the renal circulation during pregnancy. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured in conscious pregnant and virgin rats before and during infusion of 30 micrograms/min RES-701-1 (a selective ETB receptor subtype antagonist). Baseline GFR and ERPF were significantly increased by 35% in gravid rats relative to virgin controls. During infusion of RES-701-1, the pregnant rats responded more robustly, showing a greater decline in both GFR and ERPF such that renal function converged in the two groups of rats. ERPF also converged in pregnant and virgin rats during infusion of SB-209760, a nonselective ETA/B receptor subtype antagonist. Combined infusion of Nomega-nitro-L-arginine methyl ester [L-NAME, an NO synthase (NOS) inhibitor] and RES-701-1 reduced GFR and ERPF to levels comparable to those reached with either agent given alone, suggesting inhibition of a common vasodilatory pathway. RES-701-1 and SB-209670 significantly lowered the cGMP content of small renal arteries from gravid and virgin rats in vitro, strengthening the link between the renal endothelial ETB receptor subtype and NO. Importantly, we showed that RES-701-1 is not a direct inhibitor of NOS. We conclude that endothelin mediates the NO-dependent changes in the renal circulation of conscious rats during pregnancy. SN - 0002-9513 UR - https://www.unboundmedicine.com/medline/citation/10330059/Endothelin_mediates_renal_vasodilation_and_hyperfiltration_during_pregnancy_in_chronically_instrumented_conscious_rats_ L2 - https://journals.physiology.org/doi/10.1152/ajprenal.1999.276.5.F767?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -