Potential Functions of Plasma Prorenin; Regional Activation and Tissue Extraction

Thatcher, R. L.; Butty, Jill; Whitworth, Judith A.; Hunt, Vickie; Shaw, P. F.; Skinner, Sandford L.; Horowitz, J. D.

doi:10.3109/10641968709158993

Cited by 5 publications

(5 citation statements)

References 17 publications

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“…After centrifugation at 2,000g for 10 minutes, 0.9-ml aliquots of plasma were transferred to tubes containing 0.1 ml of 300 mM sodium phosphate, 25 mM Af-ethylmaleimide, 100 mM benzamidine, pH 7.4 (to prevent cryoactivation of inactive renin 32 ), then were rapidly frozen in dry ice and stored at -30°C until assay. Plasma ACE activity was measured by spectrophotometric assay using 2 mM 3-(2-furylacryloyl)-L-phenylalanyl-glycyl-glycine as substrate.…”

Section: Measurement Of Angiotensin Converting Enzyme Renin and Angmentioning

confidence: 99%

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

et al. 1991

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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).

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Section: Measurement Of Angiotensin Converting Enzyme Renin and Angmentioning

confidence: 99%

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

et al. 1991

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“…Samples of arterial and jugular blood and CSF were collected similarly. After centrifugation at 2,000 g for 10 min, 0.9 ml plasma or CSF were transferred to tubes containing 0.1 ml 300 mM sodium phosphate, pH 7.4, 100 mM benzamidine (in order to prevent cryoactivation of inactive renin [36]), then rapidly frozen in dry ice and stored at -30 °C until assay.…”

Section: Measurement O F Renin and Angiotensinogen In Plasma And Csfmentioning

confidence: 99%

Increased Angiotensin-(1–7) in Hypophysial-Portal Plasma of Conscious Sheep

Lawrence

Clark²,

Campbell³

1992

Neuroendocrinology

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Studies were undertaken to characterize angiotensin peptides in hypophysial-portal blood of conscious sheep and to determine whether the median eminence (ME) secretes angiotensin peptides into the hypophysial-portal circulation. Simultaneous measurements of angiotensin peptides in jugular and hypophysial-portal plasma were performed in 6 sheep. Cerebrospinal fluid (CSF) was collected and data for hypophysial-portal plasma were corrected for CSF contamination. Angiotensin peptides were also measured in extracts of sheep ME. In a separate group of 4 sheep, simultaneous measurements of angiotensin peptides in arterial and jugular plasma were performed. Using high performance liquid chromatography-based radioimmunoassays, 8 angiotensin peptides were measured: Ang-(1–7), Ang II, Ang-(1–9), Ang I, Ang-(2–7), Ang III, Ang-(2–9), and Ang-(2-10). Renin, angiotensinogen and prolyl endopeptidase were also measured. No differences in angiotensin peptide levels in arterial and jugular plasma were observed. Angiotensin peptide levels in hypophysial-portal plasma were similar to those in jugular plasma, except for Ang-(1–7), the levels of which were 5-fold higher in hypophysial-portal plasma, and Ang I, for which the levels in hypophysial-portal plasma were 46% of the jugular levels. Renin and angiotensinogen levels were similar in arterial, jugular, and hypophysial-portal plasma. Angiotensin peptide contents of sheep ME were < 16 fmol/ME. However, the prolyl endopeptidase content of sheep ME was 430-fold higher than plasma levels. The low levels of angiotensin peptides in sheep ME indicate that it does not secrete these peptides into the hypophysial-portal circulation. Rather, the high level of prolyl endopeptidase in ME is consistent with region-specific metabolism of Ang I delivered to the ME by arterial blood, generating increased levels of Ang-(1–7) in hypophysial portal plasma. The increased levels of Ang-(1–7) in hypophysial-portal plasma may play a role in regulation of pituitary function.

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“…The fact that it did not argues that the increase in prorenin was due to its local production and accumulation. We therefore suggest that the evidence for local prorenin production is stronger than for renin production, as also supported by the data of Thatcher et al (1987).…”

Section: Discussionmentioning

confidence: 53%

Extrarenal production and activation of human plasma prorenin: the evidence after venous occlusion

Hare

Loh²,

Osmond³

1989

Can. J. Physiol. Pharmacol.

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Venous occlusion of the left arm in consenting men was induced for 10 or 20 min to stimulate local fibrinolytic and other proteases, thereby favouring the conversion of prorenin to renin. Using the two techniques cryoactivation and tryptic activation, we found that plasma active renin increased significantly after such occlusion (10 and 20 min) while prorenin rose more convincingly and progressively from 10 to 20 min. The renin increase can be partially attributed to hemoconcentration, but in vivo production and (or) local activation of prorenin to renin cannot be excluded. The prorenin rise can apparently be attributed to local extrarenal production, and not to hemoconcentration or influx, since it was progressive and neither prorenin nor renin levels were raised at all in blood circulating outside the occluded arm. Prekallikrein and plasminogen levels were elevated in occlusion plasmas, but responsibility of these enzyme systems for any enhanced activation of prorenin was not established. The trypsin inhibitory capacity was also elevated, increasing the requirement of trypsin to achieve optimal activation of prorenin, but not changing the prorenin estimate itself. Thus, prorenin appears to be released extrarenally, within the vasculature of an occluded arm, while in vitro evidence suggests that the mechanisms for its activation were stimulated. The importance of such extrarenal production and activation of prorenin for renin production under other physiological or pathophysiological conditions remains to be determined.

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Potential Functions of Plasma Prorenin; Regional Activation and Tissue Extraction

Cited by 5 publications

References 17 publications

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

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

Increased Angiotensin-(1–7) in Hypophysial-Portal Plasma of Conscious Sheep

Extrarenal production and activation of human plasma prorenin: the evidence after venous occlusion

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