Malignant hypertension: a syndrome accompanied by plasmatic diminution of low and high molecular weight kininogens.

Abstract

Total kininogen (Kgn), kallikrein, and prekallikrein were measured in patients with malignant hypertension (MH), essential hypertension (EH), normotensive control (NC), and hypertension and chronic renal failure (HRF). These components of the kallikrein-kinin system were related to the levels of creatinine and fibrinogen. High molecular weight Kgn and low molecular weight Kgn were also measured in blood samples from a peripheral vein, arterial blood, and suprahepatic vein in NC, EH, and MH. Results showed that total Kgn levels were diminished in MH and this diminution could not be ascribed to decreases in renal function, hematocrit, or fibrinogen levels. Appropriate antihypertensive treatment for over 1 year did not normalize Kgn levels in 10 of 11 patients. High molecular weight Kgn and low molecular weight Kgn were both diminished in MH (0.26 +/- 0.04 nmol bradykinin/ml and 0.93 +/- 0.12 nmol lysyl-bradykinin/ml, respectively) as compared to NC (0.39 +/- 0.07 and 1.92 +/- 0.16) and EH (0.51 +/- 0.07 and 1.65 +/- 0.13). Higher concentrations of high molecular weight Kgn were demonstrated in the suprahepatic vein as compared to arterial blood, demonstrating its synthesis by the liver. However, patients with MH had a diminished capacity to synthetize high molecular weight Kgn. A decrease in synthesis of high molecular weight Kgn may be a partial explanation for low levels of total Kgn. It is suggested that a lack of Kgn may play a role in the pathogenesis of MH.