Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

BRAIN AND BLOOD PRESSURE IN EXPERIMENTAL ANIMALS: Our experiments in models of experimental hypertension in the rabbit in the early 1970s demonstrated that increased activity of bulbospinal pressor neurons containing noradrenaline or serotonin mediated the elevated arterial blood pressure. Other workers had demonstrated decreased activity of noradrenergic neurons in the medulla. Accordingly, I proposed the hypothesis that the hypertension in these models arose from 'disinhibition', due to unrestrained activity of descending pressor pathways, released from the inhibitory influences present in normal animals. Over the next 15-20 years, experiments from our group and from other laboratories demonstrated that there were two distinct bulbospinal pressor pathways descending from the rostral ventral medulla, one containing adrenaline, neuropeptide Y and glutamate, and the other containing serotonin, substance P and glutamate. It has also been established that the key depressor area is in the caudal ventrolateral medulla and that the main inhibitory input, restraining the activity of the bulbospinal pressor pathways, is a short gamma-aminobutyric acid (GABA) projection ascending from the caudal ventrolateral medulla to the rostral ventral medulla. More recent experiments in the spontaneously hypertensive rat (SHR) using the immediate-early gene c-fos as a marker of neuronal activity, have demonstrated that impaired activity of this short inhibitory GABA pathway in the SHR disinhibits the bulbospinal pressor pathway, thus contributing to the hypertension in this model. BLOOD PRESSURE AND STROKE IN HUMANS: The risks of primary stroke and of secondary or recurrent stroke are both directly related to the level of blood pressure and clinical trials have clearly demonstrated that lowering blood pressure markedly reduces the incidence of primary stroke. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was launched to test the hypothesis that lowering the blood pressure in subjects who have already had a stroke or a transient ischaemic attack will also reduce the risk of stroke. A major unresolved issue for practising clinicians is how to manage the raised blood pressure that is so common in the acute phase of stroke. Accordingly, the PROGRESS investigators are planning another major multinational trial to assess the benefits and risks of lowering blood pressure in the first 3 days after the onset of a stroke.
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PMID:Volhard Lecture. Brain, blood pressure and stroke. 988 69

Patients with hypertension have a high risk of ischemic stroke and subsequent stroke-associated pneumonia. Stroke-associated pneumonia is most likely to develop in patients with dysphagia. The present study was designed to compare the ameliorative effects of different treatments in rat model of dysphagia. Spontaneously hypertensive rats were treated with bilateral common carotid artery occlusion (BCAO) to induce chronic cerebral hypoperfusion causing disorders of the swallowing reflex. Angiotensin-converting enzyme (ACE) inhibitors (perindopril, imidapril and enalapril), an angiotensin II type 1-receptor blocker (losartan), a vasodilator (hydralazine) and an indirect dopamine agonist (amantadine) were dissolved in drinking water and administered to the rats for six weeks. The blood pressure, the swallowing reflex under anesthesia, the substance P content in the striatum and the tyrosine hydroxylase (TH) expression in the substantial nigra were measured. Compared to the vehicle control, the decrease in the swallowing reflex induced by BCAO was attenuated significantly by enalapril, imidapril and perindopril, but only slightly by losartan. Hydralazine had no effect on the swallowing reflex. Amantadine significantly attenuated the decreased swallowing reflex but increased the blood pressure. Cerebral hypoperfusion for six weeks decreased the TH expression and substance P level. Perindopril improved both the TH expressions and substance P level, but imidapril, enalapril and amantadine only improved the substance P level. The present findings indicate that perindopril could be useful for preventing dysphagia in the chronic stage of stroke by attenuating the decrease in TH expression and the decrease in the substance P level.
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PMID:Perindopril increases the swallowing reflex by inhibiting substance P degradation and tyrosine hydroxylase activation in a rat model of dysphagia. 2544 54