Differential regulation of angiotensin peptide levels in plasma and kidney of the rat.

Abstract

We compared the effects of the converting enzyme inhibitor perindopril on components of the renin-angiotensin system in plasma and kidney of male Sprague-Dawley rats administered perindopril in their drinking water at two doses (1.4 and 4.2 mg/kg) over 7 days. Eight angiotensin peptides were measured in plasma and kidney: angiotensin-(l-7), angiotensin II, angiotensin-(l-9), angiotensin I, angiotensin-(2-7), angiotensin III, angiotensin-(2-9), and angiotensin-(2-10). In addition, angiotensin converting enzyme activity, renin, and angiotensinogen were measured in plasma, and renin, angiotensinogen, and their respective messenger RNAs were measured in kidney; angiotensinogen messenger RNA was also measured in liver. In plasma, the highest dose of perindopril reduced angiotensin converting enzyme activity to 11% of control, increased renin 200-fold, reduced angiotensinogen to 11% of control, increased angiotensin-(l-7), angiotensin I, angiotensin-(2-7), and angiotensin-(2-10) levels 25-, 9-, 10-, and 13-fold, respectively; angiotensin II levels were not significantly different from control. By contrast, for the kidney, angiotensin-(l-7), angiotensin I, angiotensin-(2-7), and angiotensin-(2-10) levels did not increase; angiotensin II levels fell to 14% of control, and angiotensinogen fell to 12% of control. Kidney renin messenger RNA levels increased 12-fold, but renal renin content and angiotensinogen messenger RNA levels in kidney and liver were not influenced by perindopril treatment. These results demonstrate a differential regulation of angiotensin peptides in plasma and kidney and provide direct support for the proposal that the cardiovascular effects of converting enzyme inhibitors depend on modulation of tissue angiotensin systems. Moreover, the failure of kidney angiotensin I levels to increase with perindopril treatment, taken together with the fall in kidney angiotensinogen levels, suggests that angiotensinogen may be a major rate-limiting determinant of angiotensin peptide levels in the kidney. {Hypertension 1991;18:763-773)A ngiotensin II (Ang II) plays a major role in the / \ regulation of blood pressure and fluid and J. X . electrolyte homeostasis. The major pathway of Ang II formation is by the action of renin (EC 3.4.99.19) to cleave the decapeptide angiotensin I (Ang I) from angiotensinogen, 12 with subsequent cleavage of the C-terminal dipeptide from Ang V by angiotensin converting enzyme (ACE) (dipeptidyl carboxypeptidase, peptidyldipeptide hydrolase; EC 3A.IDA).

Everything we always wanted to know about furosemide but were afraid to ask

“…Activity of the systemic RAS does not always parallel activity of the intrarenal RAS (16,25,49,103). We have been unable to find any studies on kidney vs. systemic, or tubular fluid vs. systemic RAS levels during furosemide administration.…”

Aliskiren reduces vascular pathology in diabetic retinopathy and oxygen-induced retinopathy in the transgenic (mRen-2)27 rat

“…Samples were centrifuged and the plasma stored at -20°C. The enzymatic activity of active renin in the plasma was determined by incubation with rat angiotensinogen and measurement of angiotensin I generation by RIA as described by Campbell et al [26], except that the antibody-capture method for the renin assay was used to avoid overestimation of renin inhibition by aliskiren [27].…”

Kidney Aminopeptidase A and Hypertension, Part I

“…Because plasma levels of renin or Ang II do not always reflect accurately the level of activity within tissues, 11,12,16 it is not clear whether there is any functional significance to the increase in plasma APA in SHR. Further, the molecular nature of this activity has not been determined.…”