The kallikrein-kinin system is complex, with several bioactive peptides that are formed in many different compartments. Kinin peptides are implicated in many physiological and pathological processes including the regulation of blood pressure and sodium homeostasis, inflammatory processes, and the cardioprotective effects of preconditioning. We established a methodology for the measurement of individual kinin peptides in order to study the function of the kallikreinkinin system. The levels of kinin peptides in tissues were higher than in blood, confirming the primary tissue localization of the kallikreinkinin system. Moreover, the separate measurement of bradykinin and kallidin peptides in man demonstrated the differential regulation of the plasma and tissue kallikrein-kinin systems, respectively. Kinin peptide levels were increased in the heart of rats with myocardial infarction, in tissues of diabetic and spontaneously hypertensive rats, and in urine of patients with interstitial cystitis, suggesting a role for kinin peptides in the pathogenesis of these conditions. By contrast, blood levels of kallidin, but not bradykinin, peptides were suppressed in patients with severe cardiac failure, suggesting that the activity of the tissue kallikrein-kinin system may be suppressed in this condition. Both angiotensin converting enzyme (ACE) and neutral endopeptidase (NEP) inhibitors increased bradykinin peptide levels. ACE and NEP inhibitors had different effects on kinin peptide levels in blood, urine, and tissues, which may be accounted for by the differential contributions of ACE and NEP to kinin peptide metabolism in the multiple compartments in which kinin peptide generation occurs. Measurement of the levels of individual kinin peptides has given important information about the operation of the kallikrein-kinin system and its role in physiology and disease states.

Eight angiotensin peptides [angiotensin-(1-7), angiotensin II, angiotensin-(1-9), angiotensin I, angiotensin-(2-7), angiotensin-(2-8), angiotensin-(2-9), and angiotensin-(2-10)] were measured in plasma and kidney of adrenalectomized rats and estrogen-treated rats. In comparison with sham-operated rats, adrenalectomy increased plasma renin levels by 50-fold and reduced plasma angiotensinogen levels by 67%. Adrenalectomy increased plasma angiotensin peptide levels by 9- to 30-fold, but the increases in renal angiotensin peptide levels were much less than those seen for plasma. In comparison with vehicle-treated rats, estrogen treatment increased plasma angiotensinogen levels by 3-fold and reduced plasma renin levels by 41%. Estrogen treatment decreased plasma angiotensin peptide levels, whereas renal angiotensin peptide levels increased by as much as 2- to 3-fold. These results confirm the differential regulation of angiotensin peptide levels in plasma and kidney, and provide further support for the essential role of angiotensinogen in modulating plasma and tissue angiotensin peptide levels.

This study was to investigate the interaction between opposite result was obtained for clinic BP at trough, whereby the addition of amlodipine to perindopril low doses of perindopril (2 mg daily) and amlodipine (2.5 mg daily) on ambulatory blood pressure (BP), clinic reduced erect systolic BP (P = 0.036) and both supine and erect diastolic BP (P = 0.038) whereas the addition BP, serum angiotensin-converting enzyme (ACE), plasma levels of renin (PRA), angiotensin II (Ang II), of perindopril to amlodipine was without effect. The addition of perindopril to amlodipine decreased aldosterone, and atrial natriuretic peptide (␣-h ANP) in subjects with essential hypertension. The study design serum ACE by 72% and increased PRA two-fold, without change in plasma levels of Ang II, aldosterone or ␣-h was a parallel, two-period, placebo-controlled, doubleblind crossover design, with 11 subjects receiving per-ANP. The addition of amlodipine to perindopril increased plasma aldosterone 1.7-fold but did not affect indopril and 10 receiving amlodipine during the run-in phase.serum ACE, PRA, Ang II, or ␣-h ANP. These interactions between perindopril and amlodipThe addition of amlodipine to perindopril had no effect on ambulatory BP, whereas the addition of perinine may have been conditioned by the specific effects of the therapy first given, as well as by the different cirdopril to amlodipine reduced both systolic (P = 0.027) and diastolic (P = 0.049) ambulatory BP. By contrast, the cumstances of BP measurement (ambulatory vs clinic).

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