The rostral ventrolateral medulla (RVL) in the medulla oblongata contains a group of vasomotor neurons that regulate the level of arterial blood pressure. That these spinal-projecting neurons were spontaneously active, cardiac-locked and barosensitive further underlies their important role in generating a tonic sympathoexcitatory outflow. In pentobarbital anesthetized spontaneously hypertensive rats (SHR), the electrophysiological behaviours of these sympathoexcitatory cardiovascular neurons were significantly different from those of normotensive Wistar Kyoto rats (WKY). In SHR, there was an equal occurrence of slow-conducting single discharge units and fast-conducting double discharge units while the vast majority of RVL neurons was single discharge units in WKY. Further, the single discharge units of SHR had a higher firing rate and a more regular discharge pattern than those in WKY. The activity of a subpopulation of these RVL cardiovascular neurons was excited by iontophoretic application of angiotensin II, with the magnitude and duration of the excitation greater in SHR than in WKY. Besides, microinjection of [Sar1, Ile8]-angiotensin II, an angiotensin II antagonist, to RVL caused a greater decrease in the firing rate of a subpopulation of RVL cardiovascular neurons in SHR than in WKY. In both types of rats, the neuronal responses were significantly greater in double discharge units than in single discharge units. This was followed by a subsequent depressor response which was significantly greater in SHR than in WKY. These observations demonstrate that in SHR the altered spontaneous electrophysiological property of sympathoexcitatory neurons in the RVL and their augmented sensitivity to the tonic influence of brain angiotensin may contribute to the manifestation of hypertension in this strain of rats.

1992-02-01·Hypertension (Dallas, Tex. : 1979)1区 · 医学

Stimulation of endothelial cell prostaglandin production by angiotensin peptides. Characterization of receptors.

1区 · 医学

Article

作者: Chappell, M C ; Ferrario, C M ; Jaiswal, N ; Diz, D I ; Khosla, M C

Angiotensin II stimulates prostaglandin release in blood vessels via activation of angiotensin receptors present in endothelium, vascular smooth muscle cells, or both. We evaluated the response of angiotensin II, angiotensin I, and [des-Phe8] angiotensin II [angiotensin-(1-7)] on prostaglandin release in porcine aortic endothelial cells. Incubation of cell monolayers with angiotensin I and angiotensin-(1-7), but not angiotensin II, stimulated the release of prostaglandin E2 and prostaglandin I2 in a dose-dependent manner (10(-10) to 10(-6) M) with an EC50 of approximately 1 nM. In addition, we characterized the angiotensin receptor subtypes mediating prostaglandin synthesis by using subtype-selective antagonists. Angiotensin I-stimulated prostaglandin synthesis was not altered by either of the nonselective classical angiotensin receptor antagonists [Sar1,Thr8]angiotensin II or [Sar1,Ile8]angiotensin II. In contrast, either the angiotensin subtype 1 (AT1) antagonist DuP 753 or the subtype 2 (AT2) antagonist CGP42112A significantly attenuated the prostaglandin release in response to angiotensin I. However, PD123177, another AT2 antagonist, did not inhibit angiotensin I-stimulated prostaglandin release. Angiotensin-(1-7)-induced prostaglandin release was significantly attenuated by [Sar1,Thr8]angiotensin II (10(-6) M) and PD123177 (10(-6) M) but not by [Sar1,Ile8]angiotensin II, DuP 753, or CGP42112A. Higher doses (10(-5) M) of DuP 753 and CGP42112A attenuated the angiotensin-(1-7) response. These data suggest that in porcine aortic endothelial cells, angiotensin I and angiotensin-(1-7) but not angiotensin II are potent stimuli for prostaglandin synthesis.(ABSTRACT TRUNCATED AT 250 WORDS)

1991-09-01·Alcohol (Fayetteville, N.Y.)4区 · 医学

The amino acid composition of angiotensin alters its ability to reduce alcohol consumption in rats

4区 · 医学

Article

作者: L.A. Grupp ; E. Perlanski ; A.D. Ross

The voluntary consumption of alcohol has been shown to be reduced by a variety of manipulations which enhance activity in the renin-angiotensin system, including the administration of the bovine form of angiotensin II-[Val5]-ANG II. The present study investigated the relationship between the amino acid composition of angiotensin II and its ability to reduce alcohol intake by administering a number of different forms or fragments of the parent peptide. [Ile5]-Angiotensin II ([Ile5]-ANG II), two endogenous fragments of angiotensin II [( Des-Asp1]-ANG II and [Des-Phe8]-ANG II) were administered subcutaneously in rats across a range of doses. [Ile5]-ANG II reduced alcohol intake at all doses tested between 20 and 400 micrograms/kg while [Des-Asp1]-ANG II reduced alcohol intake only at the 400 micrograms/kg dose. [Des-Phe8]-ANG II had no effect on alcohol intake at any dose tested. Administration of the antagonist [Sar1-Thr8]-ANG II by itself did not enhance alcohol intake. While the pressor and dipsogenic properties of these fragments sometimes correlated with the reduction in alcohol intake they were not a causal factor in decreasing the intake. These results indicate that variations in the peptide composition of angiotensin can significantly alter its ability to reduce the consumption of alcohol.

100 项与 [Asp1-Ile5] angiotensin II 相关的药物交易

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