Pressor activity of dialyzed plasma of patients with primary and secondary (Renal) hypertension

Abstract

I N EARLY experimental renal hypertension and in patients with acute severe hypertension increased amounts of renin have been claimed to be found in renal venous and peripheral blood.1-5 In chronic hypertension in animals produced by renal ischemia and in primary hypertension and less severe forms of secondary (renal) hypertension either insignificant quantities or no renin has been recovered from the systemic blood .48 Experiments by Wakerlin and Johnson,g Helmer et al.1° and Goldblatt and co-workers” have shown that in dogs made hypertensive for prolonged periods by renal artery constriction, it is possible to produce antirenin which neutralizes renin and lowers the blood pressure. It has also been reported that the intramuscular injection of hog renin into hypertensive persons results in the production of antibodies to renin from a variety of experimental animals, but no antibodies to human renin can be detected nor is there significant lowering of the blood pressure in these patients.10-12 Furthermore, Pear@ obtained blood by bilateral renal vein catheterization in patients with malignant hypertension and unilateral renal disease and was unable to demonstrate the presence of excess renin. However, Kahn and Skeggs i4,15 have reported the presence of increased amounts of angiotensin in the arterial blood of patients with essential and malignant hypertension. Angiotensin concentration in blood from malignant hypertensive patients was greater than that in blood from primary hypertensive patients, the latter being only slightly significant when compared with the angiotensin concentrations of the normotensive group. In view of these observations the humoral renal pressor mechanisms have been investigated in human arterial hypertension by obtaining samples of blood from the renal vein and peripheral vessels, and assaying their vasoconstrictor activity by the use of spirally cut strips of rabbit thoracic aorta and their vasopressor activity by intravenous injection into the two day postnephrectomized pithed cat.i6J7 It was hoped that these rather simplified bioassay technics would prove to be more sensitive and practical than those previously described, possibly shed some light on the disturbed physiologic mechanisms in arterial hypertension and assist in the reassessment of the relative importance of the renin-angiotensin system in hypertension . Experiments by Kohlstaedt, Helmer and Pagei indicated that renin was probably an enzyme and vasoinactive. Page and Helmerig and Rraun-Menendez et aLTo showed that a substance in plasma was activated by renin to form a vasopressor substance which has now been designated angiotensin. Since then the polypeptide structure of angiotensin and its amino acid sequence have been determined by Elliott and Peartzl and Skeggs and his associates.2” Skeggs, Kahn and Shumwayz3 and Helmer?,’ have shown that angiotensin occurs in two forms: angiotensin I (decapeptide) which is inactive but is acted upon by the converting enzyme to form angiotensin n (octapeptide), the pressor substance. Angiotensin I, however, is equally active in viva in that it is rapidly converted by the converting enzyme in plasma to angiotensin n.