|
Sign In to gain access to subscriptions and/or personal tools.
|
Blunted suppression of plasma renin activity in diabetes
Michael S Gordon
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, USA
Deborah A Price
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, USA
Norman K Hollenberg
Departments of Medicine and Radiology, Brigham and Women's Hospital and Harvard Medical School, Boston, USA, djpagecapo@ rics.bwh.harvard.edu
We have documented, contrary to expectation, that the renin-angiotensin-aldosterone system (RAAS) is stimulated normally by restriction of sodium intake in patients with Type 2 diabetes mellitus (DM) and hypertension. Conversely, plasma renin activity (PRA) is suppressed less than in normal subjects by a high-salt diet in these patients. Increasing plasma angiotensin II (Ang II) concentration through intravenous Ang II infusion also suppresses renin release, via the short feedback loop. In this study, we sought to ascertain whether the limited renin suppression in Type 2 diabetes mellitus via high-salt intake is a unique defect or part of a more generalised abnormality of PRA suppression. We studied 38 patients with Type 2 DM and hypertension, 158 hypertensive control patients, and 61 normotensive controls. All patients were studied while in metabolic balance on a 10 mEq sodium (Na) diet. The response to the Ang II infusion at 3 ng/kg/min for 45 minutes was measured. We found that PRA fell significantly in normal subjects, from 4.0±0.33 to 2.5±0.23 ng AngI/ml/hr (p=0.0056). In patients with essential hypertension, the Ang II infusion also led to a fall in PRA from 3.51±0.23 to 2.76±0.17 ng AngI/ml/hr (p=0.014). In patients with DM, despite a similar basal PRA (3.7±0.40 ng AngI/ml/hr), the infusion of Ang II did not influence PRA significantly (3.43±0.42 ng AngI/ml/hr; p>0.77), though these patients had the most robust mean arterial pressure response. Our data are in complete accord with the concept of high intrarenal Ang II in DM and suggest lower systemic Ang II despite comparable PRA.
Key Words: Type 2 DM PRA angiotensin II
References
- Bjork S. The renin-angiotensin system in diabetes mellitus: A physiologic and therapeutic study. Scand J Urol Nephrol Suppl 1990;126:1-50.[Medline]
[Order article via Infotrieve]
- De'Oliveira JM, Price DA, Fisher NDL et al. Autonomy of the renin system in type II diabetes mellitus: Dietary sodium and renal hemodynamic responses to ACE inhibition. Kidney Int 1997;52:771-7.[Web of Science][Medline]
[Order article via Infotrieve]
- Price DA, De'Oliveira JM, Fisher ND et al. The state and responsiveness of the renin-angiotensin-aldosterone system in patients with type II diabetes mellitus. Am J Hypertens 1999;12:348-55.[Web of Science][Medline]
[Order article via Infotrieve]
- Bunag RD, Page IH, McCubin JW Inhibition of renin release by vasopressin and angiotensin. Cardiovasc Res 1967;1:67-73.[Abstract/Free Full Text]
- Shade RE, Davis JO, Johnson JA et al. Mechanism of action of angiotensin II and antidiuretic hormone on renin secretion. Am J Physiol 1973;224:926-43.[Free Full Text]
- Michelakis AM, Horton R. The relationship between plasma renin and aldosterone in normal man. Circ Res 1970;16/17:185-94.
- Kurtz A., Wagner C. Regulation of renin secretion by angiotensin II-AT1 receptors. J Am Soc Nephrol Suppl 1999;10:162-8.
- Shoback DM, Williams GH, Moore TJ et al. Defect in the sodium-modulated tissue responsiveness to Ang II in essential hypertension. J Clin Invest 1983;72:2115-24.[Web of Science][Medline]
[Order article via Infotrieve]
- Emanuel R., Cain JP, Williams GH Double antibody radioimmunoassay of renin activity and Ang II in human peripheral plasma. J Lab Clin Med 1973;81:632-40.[Web of Science][Medline]
[Order article via Infotrieve]
- Underwood RH,Williams GHThe simultaneous measurement of aldosterone, cortisol, corticosterone in human peripheral plasma by displacement analysis. J Lab Clin Med 1972;70:848-62.
- Trujillo A., Eggena P., Barrett J. et al. Renin regulation in type II diabetes: Influence of dietary sodium. Hypertension 1989;13:200-5.[Abstract/Free Full Text]
- Price DA, Porter LE, Gordon MS et al.The paradox of the low-renin state in diabetic nephropathy. J Am Soc Nephrol 1999;10:2382-91.[Abstract/Free Full Text]
- Seely EW, Moore TJ, Rogacz S. et al. Angiotensin-mediate renin suppression is altered in non-modulating hypertension. Hypertension 1989;13:31-7.[Abstract]
- Baretta-Piccoli C., Weidmann P. Exaggerated pressor responsiveness to norepinephrine in nonazotemic diabetes mellitus. Am J Med 1981;71:829-35.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Weidmann P., Beretta-Piccoli C., Trost BN Pressor factors and responsiveness in hypertension accompanying diabetes mellitus. Hypertension 1985;7:33-42.[Web of Science]
- Osei SY, Price DA, Fisher NDL et al. Hyperglycemia and angiotensin-mediated control of the renal circulation in healthy humans. Hypertension 1999;33:559-64.[Abstract/Free Full Text]
- Miller JA, Floras JS, Zinman B. et al. Effect of hyperglycemia on arterial pressure, plasma renin activity and renal function in early diabetes. Clin Sci 1996;90:189-95.[Web of Science][Medline]
[Order article via Infotrieve]
- Koya D., Kiein GL Protein kinase-C activation and the development of diabetic complications. Diabetes 1998;47:859-66.[Abstract]
- Ishii H., Koya D., King GL Protein kinase-C activation and its role in the development of vascular complications in diabetes mellitus.JMolMed 1998;76:21-31.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Tesfamarian B. Free radicals in diabetic endothelial cell dysfunction. Free Radic Biol Med 1994;16:383-91.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Schricker K., Kurtz A. Blockade of nitric oxide formation inhibits the stimulation of the renin system by a low-salt intake. Pflugers Arch 1996;432:187-91.[CrossRef][Web of Science][Medline]
[Order article via Infotrieve]
- Wagner C., Jensen BL, Kramer BK et al. Control of the renal renin system by local factors. Kidney Int Suppl 1998;67:78-83.
- Schricker K., Hamann M., Kurtz A. Nitric oxide and the prostaglandins are involved in the macula densa control of the renin system. Am J Physiol 1995; 269:F825-30.[Web of Science][Medline]
[Order article via Infotrieve]
Journal of Renin-Angiotensin-Aldosterone System, Vol. 1, No. 3,
252-256 (2000)
DOI: 10.3317/jraas.2000.038

CiteULike Complore Connotea Del.icio.us Digg Reddit Technorati Twitter What's this?
This article has been cited by other articles:

|
 |

|
 |
 
E. Ritz
How Little Aldosterone is Able to Raise Blood Pressure?
Clin. J. Am. Soc. Nephrol.,
April 1, 2009;
4(4):
703 - 710.
[Full Text]
[PDF]
|
 |
|
|
|