Transgenic mice overexpressing a transthyretin promoter-ANF structural fusion gene have a life-long reduction in arterial blood pressure compared to nontransgenic littermates. The present study was designed to test the hypothesis that the high plasma level of ANF in the transgenic mice inhibits the renin-angiotensin and/or vasopressin systems, thereby causing the hypotension. Mice were anaesthetized with Inactin and arterial pressure and heart rate were monitored before and during Saralasin infusion and vasopressin Vi receptor blockade. Effectiveness of the blockade was determined by injection of angiotensin and vasopressin before and during Saralasin and V] receptor antagonist administration. Saralasin was associated with hypotension in both transgenic and nontransgenic mice. The decrease in blood pressure was proportionally greater in the transgenic animals. Vasopressin receptor blockade had little effect on blood pressure in either group. Heart rates were not different between the groups during any maneuver. We conclude that the chronic hypotensive effect of ANF overproduction does not involve the inhibition of either renin-angiotensin or vasopressin systems. The data, however, suggest that the renin-angiotensin system may be stimulated in the ANF-transgenic mice.
The purpose of this study was to compare, in the same subjects, hormonal responses to 30-min head-up tilt (HUT) and lower body suction (LBNP) of different intensity (24° and 70°, and 15 and 35 mm Hg, respectively). Basal pooled individual data from -10 min (n=32) were within normal reference limits: norepinephrine (NE) averaged 318±23 pg/ml; epinephrine, 34.0±5J> pg/ml; plasma renin activity (PRA), 0.72±0.08 ng ATII/ml/h; aldosterone, 164±20 pg/ml; atrial natriuretic peptide (ANP), 29.9±2.0 pg/ml; cGMP, 6.29±0.59 mmol/1; cortisol, 95.7±5.8 ng/ml; and ACTH, 50.3±2.6 pg/ml. The low-level stimuli failed to induce consistent changes in hormone levels. From the onset of the stimulus (minute 0) to its termination (minute 30), norepinephrine (NE) increased by 101 % with LBNP-35, and by 70 % with HUT70, respectively. The NE increase with LBNP-35 was higher (p<0.05) than with HUT70. Epinephrine rose with HUT70 (by 162 %) only. PRA increased by 157 % with LBNP-35, and by 119 % with HUT70, respectively; these responses were not significantly different. Aldosterone rose equally (by 85 and 89 %) with LBNP-35 and HUT70 but not with the low-level stimuli. No consistent changes were observed in ANP, c-GMP or ACTH concentrations. Cortisol values fell during the LBNP and HUT24 situations but rose transiently after HUT70. We conclude that the hormones investigated respond differently to head-up posture and lower body suction and in a specific manner. Greater effects of high-level stimuli (HUT70, LBNP-35) were noted as compared to low-level stimuli (HUT24, LBNP-15). The application of combined sets of models stimulating the cardiovascular system may aid in the analysis of responses of hormonal systems in man.