A kallikrein-like enzyme in blood vessels of one-kidney, one clip hypertensive rats.

Abstract

Active and inactive kallikrein or a kallikrein-like enzyme are found in the aorta, vena cava, and tail artery and veins of the rat We studied the concentration of vascular ldninogenase in rats with one-kidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. Six weeks after surgery, active and total vascular kininogenase activity (active plus trypsin-activated) was measured. Blood pressure was 212±4 mm Hg in the hypertensive rats (n=33) and 120±l mm Hg in the normotensive rats (n=32) (p<0.001). Active kininogenase was lower in the hypertensive rats; although the difference was not significant in the thoracic aorta (56±8 versus 77±15), it was highly significant in the abdominal aorta (63±13 versus 167±17, p<0.001) and tail artery (48±8 versus 197±31, p< 0.003). Total vascular kininogenase activity (active plus trypsin-activated) was lower in the hypertensive rats in all arteries examined: thoracic aorta (183±16 versus 380±38, p<0.003), abdominal aorta (565+61 versus 1,093±74, p<0.001), and tail artery (532±112 versus 1,243 ± 135, p< 0.003). Active kininogenase in the vena cava was higher in the hypertensive rats (213±56 versus 131±31); however, this difference was not statistically significant, whereas in the tail veins it was highly significant (l,803±221 versus 771 ±79, p<0.003). Total venous kininogenase activity was significantly higher in the hypertensive rats (vena cava, l,850±171 versus 998±149,p<0.01; tail vein, 4,261 ±261 versus 2,521±212, p<0.001). In conclusion, we found that in rats with one-kidney, one clip renovascular hypertension both active and total vascular kininogenase are decreased in the arteries and increased in the veins. These changes may contribute to the pathogenesis of hypertension. (Hypertension 1990;16:436-440) T he kallikrein-kinin system has been implicated in the regulation of renal function and blood pressure and in the pathogenesis of various forms of hypertension. "3 We found that kallikrein or a kallikrein-like enzyme is present in the tail arteries and veins of the rat in both active and inactive (trypsin-activated) forms. Both its molecular weight and inhibition profile were similar to glandular kallikrein. It was inhibited by aprotinin and by polyclonal and monoclonal antibodies against glandular kallikrein and was resistant to soybean trypsin inhibitor (SBTI). 4 Although the function of this vascular kininogenase is not known, it could participate in circulatory homeostasis through local generation of kinins. The present study was designed to determine whether one-kidney, one clip renovascular hypertension alters the concentration of vascular kininogenase. We measured active and total kininogenase activity in the thoracic and abdominal aorta, vena cava, and tail artery and veins of rats with onekidney, one clip renovascular hypertension and in unilaterally nephrectomized normotensive rats. MethodsMale Sprague-Dawley rats weighing 200-250 g were housed in a room under conditions of constant temperature and a 12-hour light/dark cycle; ...

A kallikrein-like enzyme in the aorta of normotensive and hypertensive rats.

“…Kininogenase activity found in the aorta of normotensive rats (active, 5.1±0.4 and inactive, 230±22 pg bradykinin/mg protein per minute, n=7) was lower compared with the levels reported by Nolly et al 3 but similar to that observed by our group in homogenates of human aorta. 9 Vascular kallikrein activity is decreased in the arteries of one-kidney, one clip hypertensive rats, 5 whereas the present study indicates that it is not altered by chronic administration of Ang II. Thus, reduced vascular kallikrein activity might be typical of volume-dependent hypertension.…”

“…Oza et al 10 reported that rat vascular smooth muscle cells in culture release kinins, and vascular kininogenase activity is still present in rat vascular homogenates after endothelium removal by collagenase. 5 However, the finding that endothelial cells in culture are able to release bradykinin suggests that kallikrein may be located in both endothelial and smooth muscle cells. "…”

“…4 The observation that in one-kidney, one clip renovascular hypertension kallikrein activity is decreased in the arteries suggests that depressed formation of kinins may contribute to increased vascular resistances. 5 On the other hand, depressed kininogenase activity may be secondary to the increase in blood pressure.…”

Effects of Hoe 140, a bradykinin B2‐receptor antagonist, on renal function in conscious normotensive rats

“…Kinins are potent vasodilators, which acting as paracrine hormones, may be involved in the regulation of regional haemodynamics (Nolly et al, 1990;Saed et al, 1990;Wiemer et al, 1991;Gardiner et al, 1990;1992) and renal excretion of water and sodium (Willis et al, 1969;. Alteration of the function of locally formed kinins, leading to predominance of vasoconstrictor tone and retention of water and salt, may contribute to the pathogenesis of arterial hypertension.…”

Adenovirus-Mediated Human Tissue Kallikrein Gene Delivery Inhibits Neointima Formation Induced by Interruption of Blood Flow in Mice

“…2 In fact, vascular endothelial cells (VECs), acting as sensors of intraluminal mechanical forces, release growth factors and vasoactive substances able to induce cell proliferation, migration, and death as well as matrix deposition. 2 The presence of a local kallikrein-kinin system in the vasculature is firmly established, [4][5][6] and evidence is now emerging regarding the possible participation of this system in vascular remodeling. Tissue kallikrein is a serine protease that cleaves low molecular weight kininogen to produce kinin peptides.…”