S. F. Rabito

Evidence against a role of vasopressin in the maintenance of high blood pressure in mineralocorticoid and renovascular hypertension.

SUMMARY To determine the role of vasopressin in the maintenance of high blood pressure, the antihypertensive effect of the antagonists of the vasopressor effect of vasopressin, [l-deaminopenicillamine, 4- valine, 8-D-arginine] vasopressin (dPVDAVP), and [l-(β-mercapto-β, β-cyclopentamethylenepropionic acid), 4-valine, 8-D-arginine] vasopressin (cyclo dVDAVP), was studied in unanestfaetized, nonsurgically stressed rats with adrenal regeneration hypertension, malignant DOCA-salt hypertension, and malignant twokidney, one clip Goldblatt hypertension. The doses of vasopressin antagonist used blocked the blood pressure (BP) response to vasopressin almost completely, with no changes in the pressor response to norepinephrine and angiotensln II. Administration of the vasopressin antagonists did not induce significant changes in the mean BP in any of the three experimental groups studied. It is suggested that in unanesthetized, nonsurgically stressed rats with adrenal regeneration hypertension, malignant DOCA-salt hypertension, and malignant two-kidney, one clip Goldblatt hypertension, vasopressin does not have a role in the maintenance of high BP.

Role of the autonomic nervous system in the release of rat submandibular gland kallikrein into the circulation

We have previously demonstrated that the rat submandibular gland releases immu-noreactive kallikrein into the circulation. To study the role of the autonomic nervous system in this release, submandibular gland blood flow and kallikrein concentration in peripheral arterial and venous blood from the gland were measured and secretion rates calculated before and after parasympathetic and sympathetic nerve stimulation (8V, 2 msec, 10 Hz) for 1 minute. Immunoreac-tive kallikrein in plasma was measured by radioimmunoassay, and timed collections of venous outflow were used to measure blood flow. During basal conditions, the unstimulated submandibular gland of the rat released immunoreactive kallikrein into blood at the rate of 0.92 ± 0.07 ng/min. Parasympathetic stimulation increased blood flow 4-fold (before, 68.5 ± 8.3 μl/min; after, 253.5 ± 76.2; P < 0.05) without significantly changing immunoreactive kallikrein secretion rate. Sympathetic stimulation produced an 11-fold increase in blood flow (before, 64.9 ± 9.3 μl/min; after, 709.6 ± 97.5; P < 0.05) and a 57-fold increase in immunoreactive kallikrein secretion rate from the gland (before, 1.05 ± 0.25 ng/min; after, 59.8 ± 18.6; P < 0.05). Sympathetic stimulation also produced a 4-fold increase in the concentration of immunoreactive glandular kallikrein in arterial plasma (before, 15.2 ± 1.1 ng/ml; after, 56.2 ± 12.9; P < 0.05). Pretreatment with phentolamine (1 mg/kg) or prazosin (0.2 mg/kg) blocked the increase in kallikrein secretion rate produced by sympathetic stimulation. These results indicate that the sympathetic nervous system, through activation of oa-adrenoreceptors, controls kallikrein secretion from the submandibular gland into the circulation. Released kallikrein may be responsible for the reactive vasodilation observed in the rat submandib-ular gland after sympathetic stimulation.

Lack of evidence for the participation of tonin in the pathogenesis of one-kidney, one-clip renovascular hypertension.

It has been reported that immunization against tonin normalizes blood pressure, and that sialoadenectomy, during which the tonin-rich salivary glands are removed, decreases blood pressure in one-kidney, one-clip hypertension. To investigate the role of tonin on this form of hypertension further, we actively immunized one-kidney, one-clip hypertensive rabbits with tonin and measured both the blood pressure response and the titer of antibodies raised against tonin. In addition, because sialoadenectomy may alter food intake, we assessed the effect of sialoadenectomy on the blood pressure of one-kidney, one-clip hypertensive rats fed a liquid diet to facilitate eating. After immunization, all rabbits developed antitonin-antibody titers ranging from 1:300 to 1:56,000. However, in none of the rabbits did the blood pressure decrease significantly (114 ± 3 mm Hg before immunization; 129 ± 6 mm Hg at 16 weeks after immunization). In one-kidney, one-clip hypertensive rats, sialoadenectomy did not lower blood pressure (179 ± 5 mm Hg before sialoadenectomy; 202 ± 9 mm Hg 3 weeks after sialoadenectomy). Neither blood pressure nor body weight differed between sialoadenectomy and sham-sialoadenectomy one-kidney, one-clip hypertensive rats (n = 6). In conclusion, neither active immunization against tonin in one-kidney, one-clip hypertensive rabbits nor sialoadenectomy in one-kidney, one-clip hypertensive rats significantly reduced established hypertension. These results do not support the hypothesis that tonin is involved in the pathogenesis of one-kidney, one-clip hypertension in these animal models.

INTERFERENCE OF CONVERTING ENZYME INHIBITORS WITH THE KALLIKREIN-KININ SYSTEM

The unstimulated rat submandibular gland releases kallikrein into the circulation. This release is greatly increased by sympathetic nervous stimulation of the gland. We studied the effect of an angiotensin I converting enzyme (ACE) inhibitor (captopril) on blood flow of the unstimulated submandibular gland, and the effect of the ACE inhibitor on blood kinins and blood pressure of rats with prior sympathetic stimulation of the gland. To minimize the effects mediated by inhibition of angiotensin II formation, all rats were nephrectomized 48 hours before the studies. Administration of the ACE inhibitor caused a 2.4-fold increase in the blood flow of the unstimulated gland (p less than 0.001). Pretreatment with kinin antibodies diminished this increase by 86% (p less than 0.001). After sympathetic stimulation, blood flow to the gland increased five times, and kinin output in the venous effluent increased from 19 +/- 13 to 14,400 +/- 8,800 pg/min (p less than 0.001). Despite this conspicuous increase, arterial blood kinins did not change. Administration of the ACE inhibitor after stimulation of the gland resulted in a 10-fold increase in arterial blood kinins and in a pronounced decrease in blood pressure from 100 +/- 5 to 58 +/- 6 mmHg. This decrease was almost completely blocked by antibodies to either kallikrein or kinin. We concluded that the glandular kallikrein-kinin system may participate in the regulation of local blood flow in organs rich in glandular kallikrein such as the rat submandibular gland.(ABSTRACT TRUNCATED AT 250 WORDS)