Table 1. Comparative effects of selective enzyme inhibition on 125I-Ang-(1–12) metabolism in medium of cultured neonatal wky and shr cardiac myocytes.
Peptides | No RAS Inhibitors | +All RAS Inhibitors | Minus Lisinopril | Minus SCH39370 | Minus MLN-4760 | Minus Chymostatin |
Wistar Kyoto Rats | ||||||
Ang-(1–12)* | 26±3a | 90±2 | 41±7b | 58±4b | 92±2 | 87±3 |
Ang I | 14±1a | 4±1 | 18±5b | 7±2 | 3±1 | 5±2 |
Ang II | 37±5a | 3±1 | 33±4b | 6±3 | 2±1 | 3±1 |
Ang-(1–5) | 3±1 | 1±1 | 2±1 | 2±1 | 1±1 | 1±1 |
Ang-(1–7) | 7±2 | 1±1 | 4±1 | 7±1b | 1±1 | 1±1 |
Ang-(1–4) & smaller peptides | 13±3a | 1±1 | 2±1 | 20±2b | 1±1 | 3±1 |
Spontaneous Hypertensive Rats | ||||||
Ang-(1–12)* | 8±2a,c | 71±2c | 27±4b | 38±4b,c | 84±6 | 51±5b,c |
Ang I | 10±3 | 4±1 | 18±2b | 8±1 | 5±2 | 20±3b,c |
Ang II | 29±5a | 14±2c | 42±4b | 7±2 | 6±3 | 21±4c |
Ang-(1–5) | 6±1 | 1±1 | 3±1 | 1±1 | 2±1 | 2±1 |
Ang-(1–7) | 10±2 | 4±2 | 3±1 | 13±2b | 2±1 | 2±1 |
Ang-(1–4) & smaller peptides | 37±5a,c | 6±2 | 7±3 | 33±7b | 3±1 | 4±1 |
Values are expressed as % (Mean ± SE) of Ang-(1–12) unmetabolized* and Ang peptides (%) generated from 125I-Ang-(1–12) in the cultured medium incubated for 60 min at 37°C to WKY or SHR myocytes with or without the presence of RAS inhibitors. No inhibitors group: Only aminopeptidases inhibitors (amastatin & bestatin) and carboxypeptidases inhibitor (benzyl succinate); All inhibitors group: Aminopeptidases and carboxypeptidases inhibitors + RAS inhibitors (lisinopril, SCH39370, MLN-4760 & chymostatin); Minus RAS inhibitor groups: One of the RAS inhibitor (lisinopril/SCH39370/MLN-4760/chymostatin) omitted at a time from all inhibitors group. All values are expressed as (%) and are the average of three or more independent assays.
*Percent of 125IAng-(1–12) parent control remained un-metabolized in the medium exposed to WKY or SHR myocytes for 60 min at 37°C.
Significantly different (P<0.05) in No RAS inhibitors group vs. corresponding WKY or SHR group of +All RAS inhibitors.
Significantly different (P<0.05) vs. corresponding group of +All RAS inhibitors.
Significantly different (P<0.05) vs. corresponding WKY.