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.

1992-06-01·American Journal of Clinical Oncology4区 · 医学

Intraarterial Infusion Chemotherapy with [Sar1, Ile8]Angiotensin II for Bladder Cancer

4区 · 医学

Article

作者: Tokue, Akihiko ; Tozuka, Kazuhiko ; Ishiyama, Shunji ; Yoshikawa, Hiroyuki ; Hara, Yosuke ; Kobayashi, Yutaka ; Takahashi, Kouji ; Goto, Kentaro ; Tanaka, Osamu ; Kikuchi, Takao ; Ishikawa, Shinya ; Morita, Tatsuo

Thirty-three patients with primary bladder cancer (nine stage T1 with multifocal tumors and 24 stage T2-4) were treated with intraarterial infusion chemotherapy including cisplatin, doxorubicin, and [Sar1,Ile8]Angiotensin II(AT II). Of the 32 evaluable patients, 12 had pathologically proven complete response (CR), 19 showed partial response (PR), and one showed no change (NC); the overall response rate (CR + PR) was 97%. The blood pressure increased in response to the administration of [Sar1,Ile8]AT II in all the patients; the mean increase in the systolic blood pressure was 36 mmHg. Most of the side effects were mild to moderate in severity, transient in nature, and included nausea/vomiting (100%), alopecia (84%), leukopenia (66%), headache (9%), nephrotoxicity (6%), diarrhea (3%), skin pigmentation (3%), and neurotoxicity (3%). One patient who dropped out of the study developed hemiplegia as a result of cerebral infarction. The findings indicate that it is necessary to exercise caution in selecting the patients to be subjected to this therapy. We conclude that intraarterial infusion chemotherapy combined with a vasoconstrictor has a significant effect not only against multifocal superficial bladder cancer but also against invasive bladder cancer.

1992-02-01·Hypertension1区 · 医学

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

1区 · 医学

Article

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

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)

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

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