Role of kinin in regulation of rat submandibular gland blood flow.

Abstract

In tissues rich in kalUkrein, vasodilator kinins, acting as paracrine hormones, may play a role in the local regulation of blood flow. We studied the role of kinins in the regulation of blood flow in the rat submandibular gland using a kinin analogue with antagonistic properties, [DArg°]Hyp 3 -Thi iS [DPhe 7 ]bradykinin. When infused into the carotid artery (20 jtg/min/rat), this antagonist blocked the effect of bradykinin (25-250 ng/kg, intracarotid injection) on glandular blood flow. In nephrectomized rats, the antagonist also blocked the increase in glandular blood flow caused by enalaprilat, a kininase II converting enzyme inhibitor. At a dose of 20 /tg/min/rat, the antagonist produced no detectable change in basal glandular blood flow; however, at a higher dose (100 /ig/min/rat), it caused a significant decrease (/?<0.001). In eight of 10 rats, blood flow decreased by 75% or more; this effect was not blocked by the cv-adrenergic receptor antagonist phentolamine. After antagonist infusion was stopped, blood flow returned toward normal. Sympathetic nerve stimulation of the gland induced vasoconstriction followed by poststimulatory vasodiiatation. In rats displaying severe vasoconstriction after the antagonist, postsympathetic vasodiiatation was abolished even when stimulation was performed after the antagonist infusion had been stopped and blood flow returned toward normal. Although a direct vasoconstrictor effect of the kinin antagonist cannot be completely ruled out, these data suggest that, in the rat submandibular gland, kinins may play a role in regulation of basal blood flow and vasodiiatation after converting enzyme inhibitor or sympathetic stimulation. (Hypertension 1989;14:73-80) P otent vasodilator kinins, acting as paracrine hormones, may participate in local regulation of blood flow, possibly through activation of endothelium relaxing factor, 1 particularly in organs rich in kallikrein, 2 -7 but their role has been a subject of much controversy. 8 -9 The submandibular gland of the rat is extremely rich in kallikrein, which is released into not only saliva but also the vascular compartment. -11 Kallikrein released into blood remains sufficiently active to induce vasodiiatation in the resting gland when kinin degradation is partially blocked by captopril, a kininase II converting enzyme inhibitor (CEI). Received September 19, 1988; accepted January 23, 1989. mediated by kinins. 6 Stimulation of the sympathetic nerve causes vasoconstriction followed by poststimulatory vasodiiatation in the gland. 11- 12 We have shown that this vasodiiatation is accompanied by simultaneous release of kallikrein and kinins into the vascular compartment of the gland. 7 -10 -11 Both the poststimulatory vasodiiatation and the release of kallikrein were abolished by a-adrenergic (phentolamine) but not by /3-adrenergic (propranolol) blockade.11 These studies suggest that the kallikreinkinin system may play a role in regulation of basal submandibular gland blood flow as well as in the vasodiiatation that follows CEI ad...

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

“…Hoe 140, at a dose which significantly inhibited the hypotensive effect of exogenous bradykinin for 24 h, did not (Weipert et al, 1988;Berg et al, 1989;Carbonell et al, 1988b;Genden & Molineaux, 1991). The present study was also undertaken to determine if endogenous kinins regulate renal haemodynamics and function in unanesthetized rats.…”

Secretion of glandular kallikrein and renin from the basolateral pole of mouse submandibular duct cells: an immunocytochemical study.

“…Autonomic nerve stimulation of salivary secretion in rats causes an increase in the level of glandular kallikrein in plasma and in saliva (Berg et al, 1985;Orstavik et al, 1982) and an increased kinin concentration in the venous effluent of the submandibular gland (Berg et al, 1989). There is additional evidence to suggest that much of the glandular kallikrein in the circulation of rats originates in the salivary glands (Lawton et al,198l), where renallpancreatic kallikrein is synthesized in striated (intralobular) and excretory ducts of the submandibular (SM), sublingual, and parotid glands (Penschow et al, 1991a).…”

Influences of secretory activities in rat submandibular glands on tissue kallikrein circulating in the blood

“…The released kinins induced hypotension when the steady state between their formation and destruction was altered by nephrectomy and the administration of the kininase II inhibitor, captopril (0rstavik, Carretero, Johansen & Scicili, 1982a). In rat submandibular glands, in the presence of converting enzyme inhibitor, kinins were considered to play a role in the regulation of the basal blood flow and in a vasodilatation pursuant on sympathetic stimulation (0rstavik, Carretero & Scicli, 1982b;Berg, Carretero, Scicli, Tilley & Stewart, 1989).…”