Neuronal histamine in the gut wall releasable by gastrin and cholecystokinin

Histamine accumulated in the ligated vagus nerve of the rat, both above and below the ligature; maximum accumulation was after 4 h. The finding is suggestive of axonal flow. Further evidence for histamine in peripheral nerves was obtained in experiments showing that the guinea-pig gut wall could be labelled with [3H]histamine. The experiments were carried out with isolated strips of stomach wall and taenia coli. Electrical stimulation released [3H]histamine from these specimens. The release could be blocked by Ca2+-free medium or by tetrodotoxin. The release was unaffected by vagal denervation or chemical sympathectomy (6-hydroxydopamine) but prevented by reserpinization. Gastrin-17 and cholecystokinin-39 released radioactivity by a tetrodotoxin-sensitive mechanism. The possible existence of a gastrin/cholecystokinin-sensitive neuronal pool of histamine in the gut wall offers a new perspective on the postulated role of histamine as a physiological stimulant of gastric acid secretion and might explain why H2-receptor antagonists block gastrin-stimulated acid secretion.     

Reduced dipsogenic response induced by angiotensin II activation of subfornical organ projections to the median preoptic nucleus in estrogen-treated rats

The present study was carried out to investigate whether estrogen modulates the drinking response induced by activation of angiotensinergic neural pathways from the subfornical organ (SFO) to the median preoptic nucleus (MnPO). Microinjection of angiotensin II (ANG II, 10(-10) M, 0.2 microl) into the SFO elicited drinking in ovariectomized (OVX) female rats that were treated with either propylene glycol (PG) vehicle or estrogen benzoate (EB). The amount of water intake induced by the ANG II injection was significantly greater in the PG-treated than in the EB-treated animals. In both groups of female rats, previous injections of saralasin (Sar, 10(-10) M, 0.2 microl), a specific ANG II antagonist, into the MnPO resulted in the significant attenuation of the drinking response to ANG II, showing that the ANG II-induced drinking response may be mediated in part by the angiotensinergic SFO projections to the MnPO. Injections of ANG II (10(-10) M, 0.2 microl) into the MnPO caused drinking in both groups, while no significant difference was found between the groups in the amount of water intake. These results suggest that increases in the circulating level of estrogen may attenuate the drinking response induced by ANG II activation of the SFO projections to the MnPO.     

Cardiovascular effects of microinjections of angiotensin II into the nucleus tractus solitarii

The role of the angiotensin II system within the nucleus tractus solitarii (NTS) in central cardiovascular control was investigated by local microinjections of angiotensin II and the angiotensin II receptor antagonist saralasin. Microinjections of 1 ng angiotensin II into the NTS resulted in a monophasic depressor response (-7.3 +/- 1.7 mm Hg), while higher doses were characterized by a biphasic response, with an initial decrease followed by a subsequent increase in blood pressure (10 ng: -4.7 +/- 1.3/+7.9 +/- 1.1 and 100 ng: -2.4 +/- 1.2/+7.5 +/- 1.2 mm Hg). Heart rate decreased significantly following microinjections of 1 and 10 ng angiotensin II (-27 +/- 5.0 and -15 +/- 5.9 bpm), while with 100 ng angiotensin II there was no significant effect on heart rate. Prior i.v. administration of atropine (1 mg/kg) abolished the bradycardia, but did not significantly affect the blood pressure response. Microinjections of saralasin into the NTS elicited a dose-dependent pressor response (10 ng: 6.0 +/- 1.5 mm Hg; 100 ng: 16.8 +/- 3.4 mm Hg) and tachycardia (10 ng: 5 +/- 3.2 bpm; 100 ng: 17 +/- 4.4 bpm). Our data support the hypothesis that angiotensin II acts on specific receptors within the NTS to modulate peripheral cardiovascular responses. The cardiovascular effects elicited by microinjections of the peptide exhibit complicated dose-response relationships. The effects on heart rate, but not on blood pressure, appear to be mediated by parasympathetic activation.     

Angiotensin II (AII) modulation of steroidogenesis by luteinized granulosa cells in vitro

Purpose The purpose of the present study was to evaluate the effect of angiotensin II and its inhibitor, saralasin, on steroid production by luteinized human granulosa cells in vitro. Granulosa cells were obtained from follicular fluid aspirations from human in vitro fertilization. Cultures were established in supplemented Ham's F-10 medium. Human chorionic gonadotropin and angiotensin II were added to culture media and the effect on steroid production was measured. Results Human chorionic gonadotropin alone stimulated production of progesterone, estradiol, and testosterone. The addition of angiotensin II resulted in a dose-dependent increase in progesterone production (428% increase compared to baseline). No effect was seen on estradiol or testosterone. However, a large increase (700%) in estradiol was seen with the addition of the competitive inhibitor of angiotensin II, saralasin. Conclusion We conclude that angiotensin II modulates progesterone production by human luteinized granulosa cells in vitro. The observed enhancement of estradiol production by angiotensin blockade suggests a tonic inhibition of estradiol secretion by endogenous angiotensin II. Presented at the 36th Annual Meeting Society for Gynecologic Investigation, March, 1989, San Diego, California.     

Subfornical organ neurons with efferent projections to the hypothalamic paraventricular nucleus: an electrophysiological study in the rat

Seventeen neurons in the subfornical organ (SFO) were antidromically activated by electrical stimulation of the paraventricular nucleus (PVN) in the rat. The activity of all identified SFO neurons was excited by microiontophoretically (MIPh) applied angiotensin II (AII) and the effect of AII was blocked by MIPh-applied saralasin (Sar), an AII antagonist, but not by atropine (Atr), a muscarinic antagonist. In these identified SFO neurons, 9 were also excited and 8 were not affected by MIPh-applied acetylcholine (ACh) and the effect of ACh was attenuated by not only MIPh-applied Atr but also by Sar. These results suggest that there are specific AII- and both AII- and ACh-sensitive types of SFO neurons with efferent projections to the PVN.     

Effects of intracerebroventricular microinjection of angiotensin III on the cardiovascular activities in rabbits

Summary In mongrel rabbits intracerebroventricular microinjected angiotensin III (A III, 4 nmol) and angiotensin II (A II 4 nmol) equally evoked increase of mean arterial pressure and decrease of heart rate respectively. However, intracerebroventricular preinjection of saralasin, prazosin or arginine-vasopressin antiserum or intravenous preinjection of phentolamine could markedly attenuate the above cardiovascular effects of A III and A II respectively. The results indicated that the response intensity and mechanism of the central presser effect of A III were similar to those of A II.     

Depressive effect of morphine on the sympathetic reflex elicited by stimulation of unmyelinated hindlimb afferent nerve fibers in anesthetized cats

In conscious normotensive rats catheterized for continuous recording of blood pressure, intracerebroventricular injections of vasoactive intestinal polypeptide (VIP) produced pressor responses in contrast to depressor effects when given intravenously. The pressor effect was not mediated by angiotensin II since pretreatment with an angiotensin antagonist failed to block the response. These findings show that there are separate mechanisms for central versus peripheral effects of VIP.     

Different receptors for angiotensin II at pre- and postjunctional level of the canine mesenteric and pulmonary arteries

1. This investigation was undertaken to compare pre- and postjunctional receptors involved in the responses of the canine mesenteric and pulmonary arteries to angiotensin II.
2. In the mesenteric artery, angiotensin II caused an enhancement of tritium overflow evoked by electrical stimulation (EC_30%=5 nM), the maximal effect representing an increase by about 45%. Postjunctionally, angiotensin II caused concentration-dependent contractions (pD₂=8.57). Saralasin antagonized both pre- and postjunctional effects of angiotensin II, but it was more potent at post- than at prejunctional level (pA₂ of 9.51 and 8.15, respectively), while losartan antagonized exclusively the postjunctional effects of angiotensin II (pA₂=8.15). PD123319 had no antagonist effect either pre- or postjunctionally.
3. In the pulmonary artery, angiotensin II also caused an enhancement of the electrically-evoked tritium overflow (EC_30%=1.54 nM), its maximal effect increasing tritium overflow by about 80%. Postjunctionally, angiotensin II caused contractile responses (pD₂=8.52). As in the mesenteric artery, saralasin antagonized angiotensin II effects at both pre- and postjunctional level and it was more potent postjunctionally (pA₂ of 9.58 and 8.10, respectively). Losartan antagonized only the postjunctional effects of angiotensin II (pA₂=7.96) and PD123319 was ineffective.
4. It is concluded that in both vessels: (1) pre- and postjunctional receptors belong to a different subtype, since they are differently antagonized by the same antagonists; (2) postjunctional receptors belong to AT₁ subtype, since they are blocked by losartan but not by AT₂ antagonists; (3) prejunctional receptors apparently belong to neither AT₁ or AT₂ subtype since they are blocked by neither AT₁ nor AT₂ antagonists.