Inhibition by aspirin of the stimulated PGI2 synthesis after administration of kallikrein to hypertensive patients (new aspects of chemical pathogeny concerning the messenger systems: A and C).
The vascular smooth muscle cells belong to the category of "bidirectionally controlled cells", which can be activated (leading to contraction) by some first-messengers (such as Catecholamine-alpha 1, or Angiotensin II) in connection with a recently discovered intracellular second-messenger system-C (sms-C), namely, Diacylglycerol-dependent Protein Kinase-C + Calcium mobilization. On the other hand, these cells can be inhibited (leading to relaxation) by other first-messengers (such as Catecholamine-beta or PGI2) related to the classical "second-messenger system-A" (sms-A), namely: Ns--Adenylate Cyclase--cAMP--Protein Kinase-A. It is also known that kallikrein (via kinins) can stimulate PGI2 synthesis, and implicitly sms-A, relaxing the vascular tone by counteracting the opposite pressor effect of sms-C. In the four h samples of urine, collected before and after administration of kallikrein (i.m., 40 IU) to six hypertensive patients, we measured (RIA): 6-keto-PGF1 alpha, the stable metabolite of PGI2. The results 5.86 +/- 1.25 vs 9.94 +/- 0.6 pg/mL +/- SEM (p less than 0.05) indicate a rise in PGI2 synthesis. However, no such effect was obtained when the same patients were given aspirin (4 g in divided doses) one day before repeating the above test: 5.59 +/- 1.97 vs 6.85 +/- 1.28 (NS). We may conclude that administration of kallikrein can stimulate PGI2 synthesis, which, in turn, can be blocked by relatively high (= nocive) doses of aspirin. Some new aspects of chemical physiology, pathogeny and systematization of the two major messenger systems, MS-A and MS-C, are discussed.