PubMed Health⌕ Search

PubMed · 11459117

Adrenomedullin inhibits the pressor effects and decrease in renal blood flow induced by norepinephrine or angiotensin II in anesthetized rats.

Abstract

Adrenomedullin (AM), a hypotensive peptide originally isolated from human pheochromocytoma, has been reported to regulate renal functions. In patients with glomerulonephritis, the serum levels of AM are elevated as well as hypertensive agents norepinephrine (NE) and angiotensin II (AII). The effects of AM on the NE- or AII-induced pressor effects and renal blood flow responses, however, are not well clarified. We examined the effects of AM on blood pressure and renal blood flow induced by NE or AII in anesthetized rats. Arterial blood pressure and renal blood flow were measured using a calibrated pressure transducer and a laser Doppler flowmeter, respectively. Drugs were injected into the tail vein with a syringe. Intravenous administration of AM (1-3 nmol/kg) decreased the arterial blood pressure in anesthetized rats in a dose-dependent manner, whereas it did not affect the renal blood flow. NE or AII administration in anesthetized rats caused both increases in blood pressure and decreases in renal blood flow. Simultaneous administration of AM with NE or All prevented the increasing effects of blood pressure and inhibited the decreases in renal blood flow caused by NE or AII. These findings suggest that AM may have a protective role against the pressor effects and decrease in renal blood flow caused by NE or AII.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

K Minami, K Segawa, Y Uezono, Y Shiga, M Shiraishi, J Ogata, A Shigematsu. 2001. Adrenomedullin inhibits the pressor effects and decrease in renal blood flow induced by norepinephrine or angiotensin II in anesthetized rats.. https://doi.org/10.1254/jjp.86.159

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Lack of adrenomedullin on antigen-induced bronchoconstriction in guinea pigs in vivo.

Antigen challenge can provoke acute bronchoconstriction, recognized as immediate asthmatic response (IAR), but the evolving events in this reaction are not well defined. Recently, a novel peptide, designated adrenomedullin, was isolated from human pheochromocytoma, and has been shown to have potent systemic and pulmonary vasodilator activity.The purpose of this study was to elucidate the influence of adrenomedullin in the development of IAR. Passively sensitized guinea pigs were anesthetized and treated with diphenhydramine hydrochloride, and then artificially ventilated. Ovalbumin was inhaled after an intravenous administration of adrenomedullin. Other studies were performed in naive guinea pigs to investigate the airway responses to inhaled methacholine or histamine after an intravenous administration of adrenomedullin. Antigen challenge caused bronchoconstriction in sensitized guinea pigs. Adrenomedullin did not inhibit the antigen-induced bronchoconstriction in sensitized guinea pigs or the dose-dependent responses to inhaled methacholine or histamine in naive animals in spite of its vasodilating effect. We conclude that an intravenous administration of adrenomedullin does not influence antigen-induced bronchoconstriction or bronchial responsiveness to inhaled methacholine or histamine in vivo.

Adrenomedullin↗

Adrenomedullin stimulates somatostatin and thus inhibits histamine and acid secretion in the fundus of the stomach.

Adrenomedullin has recently been localized to enterochromaffin-like (ECL) and chief cells in the gastric fundus. It has been proposed that adrenomedullin may play a role in gastric mucosal defense and repair. In the present study, we have used the isolated, luminally perfused mouse stomach and superfused rat fundic segments to examine the effect of adrenomedullin on exocrine and endocrine secretion in this region of the stomach. Addition of adrenomedullin (1 pM to 1 microM) to the isolated mouse stomach caused a concentration-dependent decrease in acid secretion. The EC(50) value was 1.4 x 10(-9) and maximal inhibition of acid secretion was obtained at a concentration of 1 microM (31+/-4% below basal level, P<0.001). In rat fundic segments, superfusion with adrenomedullin (0.1 pM to 0.1 microM) caused a concentration-dependent increase in somatostatin secretion (EC(50), 1 x 10(-10)) that was accompanied by a reciprocal decrease in histamine secretion (EC(50), 1.2 x 10(-11)). Maximal stimulation of somatostatin secretion (60+/-5% above basal level, P<0.001) and inhibition of histamine secretion (50+/-5% below basal level, P<0.01) was obtained at a concentration of 0.1 microM. Changes in acid and histamine secretion induced by adrenomedullin reflected changes in somatostatin secretion and could be abolished by addition of somatostatin antibody. The axonal blocker, tetrodotoxin, also abolished the somatostatin and, consequently, the acid and histamine responses to adrenomedullin, implying that the effect of adrenomedullin on somatostatin secretion was mediated via activation of intramural neurons. We conclude that adrenomedullin, acting via intramural fundic neurons, stimulates somatostatin and thus inhibits histamine and acid secretion. This represents one mechanism by which adrenomedullin might enhance mucosal defense and repair.

Adrenomedullin↗

Adrenomedullin antagonist suppresses in vivo growth of human pancreatic cancer cells in SCID mice by suppressing angiogenesis.

Since it is reported that adrenomedullin (AM) upregulated by hypoxia inhibits hypoxic cell death, we examined the effects of AM antagonist (AM C-terminal fragment; AM(22-52)) on the growth of pancreatic cancer cells. We, for the first time, demonstrated that AM antagonist significantly reduced the in vivo growth of the pancreatic cancer cell line. Immunohistochemical analysis demonstrated that the mean diameter of blood vessels was significantly smaller in the tumor tissues treated with AM antagonist than in those treated with AM N-terminal fragment (AM(1-25)), and that the PCNA-labeling index was lower in the former than in the latter. Then we demonstrated that AM antagonist showed no effect on the in vitro growth of the pancreatic cancer cell line. These results showed that AM played an important role in the growth of pancreatic cancer cells in vivo, suggesting that AM antagonist might be a useful tool for treating pancreatic cancers.

Adrenomedullin↗