The serial changes in systemic and renal hemodynamics, water and electrolyte balances and various vasoactive hormones were examined in 12 conscious dogs before, during (10 days) the administration of dexamethasone (DEX: 0.5 mg/kg/day) and after the cessation of DEX. In addition, during the administration of DEX, pressor responses to angiotensin II, norepinephrine, an angiotensin II analogue, saralasin, and an alpha-1-blocker, prazosin, were studied. Abrupt elevation of blood pressure to 106 +/- 5 mmHg on Day 1 (vs. 91 +/- 6 mmHg control: P less than 0.05) associated with marked increases in total peripheral resistance (P less than 0.01) was shown in DEX treated animals. Accompanied with these changes, renal blood flow increased to 146 +/- 12 ml/min (vs. 103 +/- 8 ml/min control: P less than 0.05) on Day 1 and maintained. In contrast, the results of serial alterations in hormones could not show any significant changes except significant elevations in atrial natriuretic peptide and reductions of cortisol and arginine vasopressin. Also, marked natriuresis and diuresis were observed in DEX administration dogs. Pressor response to norepinephrine was significantly increased and administration of either saralasin and prazosin significantly reduced the blood pressure of DEX treated animals. These results in DEX-treated conscious dogs confirmed our previous findings in human and rats. Glucocorticoid-induced hypertension mainly depends on the increases in total peripheral resistance but not volume factors.

This study examined the effects of calcitonin gene-related peptide (CGRP) on aldosterone secretion both in vivo and in vitro. Intravenous administration of CGRP (0.01 micrograms/kg) in 6 conscious dogs produced a significant decrease in plasma aldosterone concentration from 68 +/- 12 pg/ml to 28 +/- 11 pg/ml (p less than 0.05) despite a mild but significant elevation of plasma renin activity. In an in vitro study using isolated rabbit adrenal glomerulosa cells CGRP reduced the basal aldosterone secretion in a dose-related manner and furthermore 10(-9) M CGRP inhibited the aldosterone secretion stimulated by 10(-8) M angiotensin II. From these results it is suggested that CGRP has an inhibitory effect on aldosterone secretion.

No abstract

The effects of a small dose (2 pmol/kg) of human calcitonin gene-related peptide I on plasma renin activity and hormones, including, aldosterone, ACTH, cortisol, AVP and ANH, were investigated in 14 conscious dogs. In addition, we studied the effects of calcitonin gene-related peptide on aldosterone secretion when it is stimulated by angiotensin II and ACTH. An intravenous bolus injection of 2 pmol/kg of calcitonin gene-related peptide raised plasma renin activity (by 216%, p<0.05), ACTH (by 85%, p<0.05), AVP (by 89%, p<0.05), and ANH (by 36%, p<0.05). Despite the elevation of plasma renin activity, aldosterone was decreased (by 52%, p<0.05). Cortisol did not change significantly. Infusion of 1 pmol \m=.\kg\m=-\1 \m=.\min\m=-\1of angiotensin II produced an elevation of aldosterone (by 186%, p<0.01), which was completely inhibited by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. On the other hand, aldosterone secretion stimulated by ACTH was not altered significantly by pretreatment with an injection of 2 pmol/kg of calcitonin gene-related peptide. These results suggest that calcitonin gene-related peptide inhibits aldosterone secretion, especially when aldosterone is stimulated by angiotensin II. In addition, calcitonin gene-related peptide may be involved as an endocrine modulator in the physiological control of other several hormones closely related to the hemodynamics.Calcitonin gene-related peptide (CGRP) is a 37-amino acid polypeptide that results from the tissuespecific processing of the primary RNA transcript of the calcitonin gene (1). CGRP is detected in the systemic circulation (2,3), and the plasma level of CGRP increases during normal human pregnancy (4), in endotoxemia (5) or after sensory nerve injury (6).CGRP has been reported to have a potent vasodilatory action on various isolated vascular tissue preparations (7-9). Intravenous administration of CGRP induced potent dose-related hypotensive and tachycardiac responses in rats and human sub¬ jects (10,11).In addition to its potent vasoactive property, CGRP has an effect on hormonal regulation. CGRP immunoreactivity and specific binding sites for the peptide have been detected in the heart, the adre¬ nal gland, the hypothalamus and the pituitary gland as well as in other organs (12,13). CGRP was shown to stimulate renin secretion both in normal human subjects and in rat renal juxtaglomerular cells (14). More recently CGRP has been found to exhibit stimulatory effects on ANH secretion in vitro in the isolated rat atria (15,16). More recently, we reported that CGRP had an inhibitory action on aldosterone secretion in isolated glomerulosa cells (17). However, possible interaction of CGRP with angiotensin II and ACTH on the adrenal gland in vivo received little attention. Therefore, this study was designed to examine the endocrine responses to intravenous administration of a small dose of CGRP with a specific focus on adrenal hormones, especially aldosterone, in conscious dogs.

To examine the relationships between the central and peripheral renin angiotensin system in normotensive Wistar Kyoto (WKY) rats, two-kidney, one-clip Goldblatt renovascular hypertension (RVH), spontaneously hypertensive rats (SHR), SQ 14225 (captopril) was administered intraventricularly (IVT) and intravenously (IV) in the alternative manner and their combination. Also, the effects of IVT captopril on the peripheral sympathetic nervous system were evaluated using an intravenous injection of prazosin. IVT captopril induced a significant reduction of blood pressure in both types hypertensive rats but not in normotensive rats. Greater depressor effects of IV captopril not IV prazosin following IVT captopril were observed in RVH compared to those in SHR. These results indicate that the pressor action of the brain renin angiotensin system is closely related with the sympathetic nervous system in hypertensive conditions and that these functions are independent from the peripheral renin angiotensin system. Furthermore, their roles were different in different types of experimental hypertension in rats.