Cardiac Renin levels are not influenced by the amount of resident mast cells.
To investigate whether mast cells release renin in the heart, we studied renin and prorenin synthesis by such cells, using the human mast cell lines human mastocytoma 1 and LAD2, as well as fresh mast cells from mastocytosis patients. We also quantified the contribution of mast cells to cardiac renin levels in control and infarcted rat hearts. Human mastocytoma 1 cells contained and released angiotensin I-generating activity, and the inhibition of this activity by the renin inhibitor aliskiren was comparable to that of recombinant human renin. Prorenin activation with trypsin increased angiotensin I-generating activity in the medium only, suggesting release but not storage of prorenin. The adenylyl cyclase activator forskolin, the cAMP analogue 8-db-cAMP, and the degranulator compound 48/80 increased renin release without affecting prorenin. Angiotensin II blocked the forskolin-induced renin release. Angiotensin I-generating activity was undetectable in LAD2 cells and fresh mast cells. Nonperfused rat hearts contained angiotensin I-generating activity, and aliskiren blocked approximately 70% of this activity. A 30-minute buffer perfusion washed away >70% of the aliskiren-inhibitable angiotensin I-generating activity. Prolonged buffer perfusion or compound 48/80 did not decrease cardiac angiotensin I-generating activity further or induce angiotensin I-generating activity release in the perfusion buffer. Results in infarcted hearts were identical, despite the increased mast cell number in such hearts. In conclusion, human mastocytoma 1 cells release renin and prorenin, and the regulation of this release resembles that of renal renin. However, this is not a uniform property of all mast cells. Mast cells appear an unlikely source of renin in the heart, both under normal and pathophysiological conditions.
Krop
Manne
M
Division of Pharmacology, Vascular and Metabolic Diseases, Department of Internal Medicine, Room EE1418b, Erasmus MC, Dr Molewaterplein 50, 3015 GE Rotterdam, the Netherlands.
van Veghel
Richard
R
Garrelds
Ingrid M
IM
de Bruin
René J A
RJ
van Gool
Jeanette M G
JM
van den Meiracker
Anton H
AH
Thio
Marco
M
van Daele
Paul L A
PL
Danser
A H Jan
AH
D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000803:Angiotensin I / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D008407:Mast Cells / Q000166:cytology / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000378:metabolism; D011336:Probability; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
D000803:Angiotensin I; D012083:Renin