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A local kallikrein-kinin system is present in rat hearts
H Nolly1, L A Carbini, G Scicli
1Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, MI 48202.
Insights
The heart possesses its own kallikrein-kinin system, independent of external factors. This system actively releases kallikrein, suggesting a crucial role in cardiac function and potential therapeutic targets.
Area of Science:
- Cardiovascular Physiology
- Biochemistry
Background:
- Kinins contribute to cardiac benefits from angiotensin-converting enzyme inhibitors.
- The existence of an independent cardiac kallikrein-kinin system remains unconfirmed.
Purpose of the Study:
- To investigate the presence and activity of an intrinsic kallikrein-kinin system within the heart.
- To determine if cardiac tissue synthesizes and releases kallikrein.
Main Methods:
- Measurement of kallikrein release from isolated heart slices and cultured cardiocytes.
- Analysis of tissue kallikrein mRNA using reverse transcription polymerase chain reaction (RT-PCR).
- Assessment of kallikrein activity inhibition by specific antibodies and protein synthesis inhibitors.
Main Results:
- Heart slices released active and total kallikrein into the incubation medium.
- Tissue kallikrein mRNA was detected in both atrial and ventricular cardiac tissue.
- Kallikrein activity was confirmed in cultured atrial and ventricular cardiocytes.
- Puromycin, a protein synthesis inhibitor, significantly reduced kallikrein release.
Conclusions:
- The heart harbors an independent kallikrein-kinin system.
- Cardiac tissue synthesizes and releases kallikrein, indicating its local role.
- This intrinsic system represents a potential target for cardiovascular therapies.
Abstract:
It has been reported that kinins mediate part of the beneficial cardiac effects induced by treatment with angiotensin-converting enzyme inhibitors in situations such as ischemia-reperfusion injury, myocardial infarction, and cardiac hypertrophy. However, it is not known whether the heart contains an independent kallikrein-kinin system. We measured kallikrein in tissue and in the incubation medium of heart slices. Heart slices released active and total (trypsin-activatable) kallikrein into the medium (46 +/- 5 and 380 +/- 18 pg bradykinin/mg, respectively, after 1 hour and 78 +/- 6 and 654 +/- 14 pg bradykinin/mg after 2 hours, n = 7). Release was not due to tissue damage because lactate dehydrogenase, a cytosolic marker, decreased from 8.9 +/- 2.9 to 2.9 +/- 1.0 U/mg per hour. Although kallikrein was released, total tissue kallikrein in the slices did not change (423 +/- 25 pg bradykinin/mg in nonincubated slices and 370 +/- 42 pg bradykinin/mg after 2 hours, P = NS), suggesting pool replenishment. Cardiac kallikrein activity was inhibited by incubation with anti-glandular kallikrein antibodies. Pretreatment with the protein synthesis inhibitor puromycin (10 mg IP) lowered release of active kallikrein from 78 +/- 6 to 22 +/- 4 pg bradykinin/mg and total kallikrein from 654 +/- 14 to 113 +/- 9 pg bradykinin/mg (P < .001). By using reverse transcription polymerase chain reaction with kallikrein family oligonucleotide primers and a specific kallikrein probe, we found that mRNA for tissue kallikrein is present in both atrial and ventricular RNA. Kallikrein activity was also detected in primary cultures of neonatal rat atrial and ventricular cardiocytes and their incubation medium.(ABSTRACT TRUNCATED AT 250 WORDS)