This Article Full Text Full Text (PDF) All Versions of this Article: 50/5/958    most recent HYPERTENSIONAHA.107.092973v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ahmed, F. Articles by Carey, R. M. Search for Related Content PubMed PubMed Citation Articles by Ahmed, F. Articles by Carey, R. M. Related Collections Animal models of human disease Other hypertension

(Hypertension. 2007;50:958.)
© 2007 American Heart Association, Inc.

Original Articles

Extracellular Renal Guanosine Cyclic 3'5'-Monophosphate Modulates Nitric Oxide– and Pressure-Induced Natriuresis

From the Division of Endocrinology and Metabolism, Department of Medicine, University of Virginia Health Sciences Center, Charlottesville.

Correspondence to Dr Robert M. Carey, P.O. Box 801414, University of Virginia Health System, Charlottesville, VA 22908-1414. E-mail rmc4c{at}virginia.edu

This study addresses the hypothesis that NO- and pressure-induced natriuresis are inhibited when guanosine cyclic 3',5'-monophosphate (cGMP) is prevented from being transported outside its renal synthesizing cells in vivo. Rats received a renal interstitial (RI) infusion of NO donor S-nitroso-N-acetylpenicillamine (SNAP) or SNAP+organic anion transporter inhibitor probenecid (PB) or SNAP+PB+cGMP. SNAP alone increased U_NaV (P<0.05 at 1 hour and P<0.005 at 2 hours). In contrast, SNAP failed to increase U_NaV when coinfused with PB, but cGMP coinfused with SNAP+probenecid restored the natriuretic response. SNAP alone increased RI cGMP (P<0.05) during the second experimental period. PB abolished the increase in RI cGMP in response to SNAP (P<0.01), but cGMP levels were restored by coinfusion with cGMP. PB also abolished SNAP-induced increases in fractional excretion of Na⁺ (FE_Na) and lithium (FE_Li) (both P<0.01). PB also abolished the rise in RI cGMP and natriuresis induced by raising renal perfusion pressure (RPP) from 100 to 160 mm Hg in rats subjected to a standard pressure-natriuresis protocol and the natriuretic response was rescued by coinfusion with cGMP. RI administration of phosphodiesterase type V (PDE V) reduced both RIcGMP and U_NaV in parallel (both P<0.01) without altering RIcAMP. The data demonstrate that export of cGMP from its renal synthesizing cells into the extracellular RI compartment is critical for the natriuretic action of NO donor SNAP or increased RPP and that RI cGMP controls basal Na⁺ excretion. Extracellular cGMP modulates NO- and pressure-induced natriuresis.

Key Words: sodium • cyclic GMP • nitric oxide • pressure-natriuresis • kidney • interstitial fluid • probenecid

This article has been cited by other articles:

				D. C. Lieb, B. A. Kemp, N. L. Howell, J. J. Gildea, and R. M. Carey Reinforcing Feedback Loop of Renal Cyclic Guanosine 3' 5' -Monophosphate and Interstitial Hydrostatic Pressure in Pressure-Natriuresis Hypertension, December 1, 2009; 54(6): 1278 - 1283. [Abstract] [Full Text] [PDF]

				A. Sipos, S. L. Vargas, I. Toma, F. Hanner, K. Willecke, and J. Peti-Peterdi Connexin 30 Deficiency Impairs Renal Tubular ATP Release and Pressure Natriuresis J. Am. Soc. Nephrol., August 1, 2009; 20(8): 1724 - 1732. [Abstract] [Full Text] [PDF]

				D. H. Lee, A. D. M. Riquier, L. E. Yang, P. K. K. Leong, A. B. Maunsbach, and A. A. McDonough Acute hypertension provokes acute trafficking of distal tubule Na-Cl cotransporter (NCC) to subapical cytoplasmic vesicles Am J Physiol Renal Physiol, April 1, 2009; 296(4): F810 - F818. [Abstract] [Full Text] [PDF]

				D. Zhao and L. G. Navar Acute Angiotensin II Infusions Elicit Pressure Natriuresis in Mice and Reduce Distal Fractional Sodium Reabsorption Hypertension, July 1, 2008; 52(1): 137 - 142. [Abstract] [Full Text] [PDF]