Role of kallikrein in the hypertensive effect of captopril after sympathetic stimulation of the rat submandibular gland.

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Abstract
After cervical sympathetic nerve stimulation, the rat submandibular gland releases a significant amount of kallikrein into the circulation. To determine whether this glandular kallikrein has kininogenase activity (kinin-generating capabilities) in the peripheral circulation and whether it plays a role in blood pressure regulation, the effect of captopril on blood pressure in 48 h-nephrectomized rats with and without prior sympathetic stimulation of the submandibular gland was studied. Administration of captopril 10 minutes after gland stimulation resulted in a mean blood pressure decrease (.DELTA. BP) of 43 .+-. 8.3 mm Hg (P < 0.01), whereas the BP did not decrease significantly in the rats in which the gland was not stimulated (.DELTA. BP -3.3 .+-. 0.5; P > 0.05). To confirm that the effect of captopril was due to a blockage of kinin destruction generated by glandular kallikrein and not to the inhibition of angiotensin II formation, the effect of captopril after gland stimulation was determined in rats pretreated with either IgG from nonimmunized rabbits (normal-IgG), or IgG from rabbits immunized against kinins (antikinin-Ig) or kallikrein (antikallikrein-IgG). Normal-IgG did not significantly alter the hypotensive effect of captopril (.DELTA. BP -30 .+-. 7.7; P < 0.01), while pretreatment with antikinin or antikallikrein almost completely blocked its hypotensive effect (.DELTA. BP -5.8 .+-. 1.9 and -6.4 .+-. 0.4, respectively). In the latter 2 groups, the decrease in BP was significantly smaller (P < 0.001) than in the groups that were not pretreated or in the group pretreated with normal-IgG. Aparently upon adrenergic stimulation of the submandibular gland, glandular kallikrein released into the vascular compartmemt has kininogenase activity in the peripheral circulation. The kinins released by glandular kallikrein induced hypotension when their breakdown was prevented by the kininase II inhibitor, captopril. Kinins may be responsible in part for the antihypertensive effect of captopril in situations in which glandular kallikrein in blood is increased.