The effect of hemorrhagic hypotension on urinary kallikrein excretion, renin activity, and renal cortical blood flow in the pig.

Abstract

SUMMARY We measured urinary kallikrein by its esterolytic and kinin-forming activity in 5-minute urine samples obtained throughout continuous bleeding experiments in pigs to correlate possible changes in urinary kallikrein excretion during hemorrhagic hypotension with renin activity and renal cortical blood flow. Renin activity was determined in venous blood samples and renal cortical blood flow was estimated by the radiolabeled microsphere technique. The rate of urinary kallikrein excretion was increased about 4-fold within an arterial pressure range of 100-70 mm Hg, whereas below 70 mm Hg, arterial pressure urinary kallikrein activity declined to undetectable values. Renin activity was increased only 2-fold in the arterial pressure range between 100 and 70 mm Hg but was increased 4-fold at pressures below 70 mm Hg. The pressure range of 100 to 70 mm Hg corresponded to the autoregulation of renal cortical blood flow and glomerular filtration rate; below that pressure range, renal cortical blood flow dropped to about 10% of the initial value. Therefore, it seems that urinary kallikrein is activated mainly during the period of autoregulation, whereas renin activity is, in the main, increased below the autoregulatory range of pressure. The vasodilatory urinary kallikrein kinin system might be involved in maintaining sufficient local blood flow during autoregulation whereas a decrease in blood pressure below the autoregulatory range leads to a major increase in renin activity, thus illustrating the attempt of the organism to reestablish sufficient blood pressure to maintain autoregulation. Circ Res 48: [386][387][388][389][390][391][392] 1981 Kallikreins, the enzymes that release vasoactive kinin polypeptides from kininogen substrate, are found in plasma and in organs such as pancreas, salivary glands and kidneys. Because urinary kallikrein (Urokallikrein) is functionally and structurally similar to the kallikrein found in the kidney (Nustad and Vaaje, 1975) and kidney cell suspensions (Kaizu and Margolius, 1975), it is thought that urinary kallikrein is synthesized and secreted by the kidney. Urinary kallikrein levels are abnormal in pathological conditions such as essential hypertension (Margolius et al., 1971) and primary aldosteronism (Margolius et al., 1971). The secretion of kallikrein can be altered by changes in perfusion pressure (Bevan et al., 1974;Keiser et al., 1976),

Urinary kallikrein excretion during inhibition of endogenous angiotensin II in the pig

“…However, it is possible that this particular effect is mediated by binding to a different All receptor or to the high affinity binding sites for AIII, which are less effectively occupied by saralasin (Devynck & Meyer, 1978). The fact that the peak in kallikrein excretion precedes that of PRA, as seen previously (Maier et al, 1981;, indicates that such a mechanism is also unlikely.…”

“…The vasoconstricting RAS is, therefore, in several ways linked to the vasodilator kallikrein-kinin-system and it has even been suggested that these two vasoactive systems might be regulated simultaneously (Misumi et al, 1983). In our previous studies on haemorrhagic hypotension in pigs we found increased excretion of urinary kallikrein within the arterial pressure range of 100 to 70 mm Hg, which corresponded to the relative maintenance of renal cortical blood flow (RCBF) and glomerular filtration rate (GFR) (Maier et al, 1981). Since the increase in kallikrein excretion during haemorrhagic hypotension was always accompanied by increased plasma renin activity, it is possible that the observed kallikrein increase was a consequence of elevated endogenous All induced by haemorrhage.…”

“…Renal cortical blood flow (RCBF) was evaluated in all pigs by means of radioactively labelled microspheres (15pm size, 3M Company, St. Paul, MN) as previously described in detail (Maier et al, 1981). RCBF was determined at the end of the control period and at 100, 90, 80, 70, and 60 mm Hg during bleeding experiments and is expressed as ml g-' kidney wet weight min '.…”

Changing Basal and Stimulated Activity of the Renin‐angiotensin System During the Second Half of Gestation in the Anaesthetized Piglet

“…The increase in fetal plasma renin and angiotensin II concentrations after blood loss were consistent with the possibility that the renin-angiotensin system plays a role in the restoration of blood pressure in the fetus of this species also. Sharply increased renin activity was seen in the plasma of young post-natal pigs (Maier, Starlinger, Wagner, Meyer & Binder, 1981) when the reduction in their blood pressures came into the range experienced before birth (Macdonald et al , 1983.…”

Effects of Antiproteases (Aprotinin and Gabexate-Mesilate) on the Postischemic Vascular Response of the Kidney

“…The increase in prostaglandin E2 outflow in venous renal blood after short-term normothermic ischemia [17] and the elevated urinary kallikrein excretion produced by renal hypoxia in hypovolemic pigs [18] suggest that the postischemic hyperemia following short-term normo thermic ischemia may at least in part be induced by kal likrein and/or prostaglandins. Kallikrein is known to have a twofold action: by way of kinin formation it has a vasodilating effect on the smooth muscle cells of the ves sels walls, and it activates prostaglandin synthesized in the kidneys, which in turn may induce vasodilatation [19].…”