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

Several neuropeptides cause mild flushing when infused intravenously in humans. However, only calcitonin gene-related peptide (CGRP), vasointestinal peptide, and substance P (SP) cause reproducible falls in blood pressure when infused into normal subjects. Of these, CGRP is of the most interest because it is the most potent and because it is present in vascular nerve endings. This paper summarises the evidence to date suggesting that CGRP release from vascular nerve endings may be of physiological importance in the regulation of blood pressure.
J Cardiovasc Pharmacol 1987
PMID:Clinical pharmacology of vasodilator peptides. 245 96

Endothelial cells are known to contain both soluble and particulate guanylate cyclase, but the functional role of cyclic guanosine monophosphate (cGMP) in endothelial cells remains unknown. We have investigated the effects of 8-bromo-cGMP on endothelium-dependent relaxations to acetylcholine, substance P, ATP, and the calcium ionophore A23187, and on endothelium-independent relaxations to sodium nitroprusside and glyceryl trinitrate (GTN). The ability of each of these agents to relax phenylephrine-preconstricted rings of rabbit aorta was tested in the absence and presence of 8-bromo-cGMP. In the presence of 8-bromo-cGMP, a greater concentration of phenylephrine had to be used to produce a similar level of tone and then endothelium-dependent relaxations to acetylcholine and substance P were inhibited, whereas endothelium-dependent relaxations to ATP and A23187 were unaffected. Endothelium-independent relaxations to sodium nitroprusside and GTN were only inhibited at the highest concentrations of nitroprusside and GTN. These results suggest that: (a) increasing GMP levels in endothelial cells inhibit agonist-induced release of endothelium-derived relaxing factor (EDRF); (b) a negative feedback mechanism may exist whereby EDRF stimulates soluble guanylate cyclase in endothelial cells to inhibit its own release; and (c) ATP does not induce EDRF release via phosphoinositol hydrolysis.
J Cardiovasc Pharmacol 1988 Dec
PMID:Release of endothelium-derived relaxing factor is inhibited by 8-bromo-cyclic guanosine monophosphate. 246 85

In conscious freely moving rats, administration of 0.65 to 32.5-nmol doses of substance P (SP) into the intrathecal (i.th.) space at the T8-T10 level of the spinal cord increased both mean arterial pressure (MAP) and heart rate (HR) in a dose-related manner. Concomitant with these cardiovascular effects, behavioral responses were observed. Injection of the peptide produced agitation of the rat for approximately 1 min as well as intermittent reciprocal hindlimb scratching which lasted for 3-6 min. The cardiovascular responses elicited by SP (6.5 nmol) were not blocked by systemic pretreatment with morphine (3-6 mg/kg), and the effect of SP on HR was potentiated by an i.th. dose of morphine (10 micrograms) given prior to the injection of SP. A systemic dose of phentolamine (1 mg/kg) blocked the pressor response and a depressor effect appeared, whereas propranolol (1 mg/kg) blocked the HR response. Although catecholamines mediate the spinal action of SP on MAP and HR, bilateral adrenalectomy of the rat 48 h prior to experimentation failed to affect the cardiovascular responses to SP. After transection of the spinal cord at the C3-C4 level, the hindlimb scratching behavior and the pressor response to SP were unaffected but the peak HR response was significantly reduced. These results demonstrate that the rise in MAP and HR evoked by SP is not secondary to perception of a noxious stimulus by the rat and that adrenal medullary catecholamines are not essential for these cardiovascular effects.(ABSTRACT TRUNCATED AT 250 WORDS)
J Cardiovasc Pharmacol 1989 Apr
PMID:Cardiovascular responses induced by intrathecal substance P in the conscious freely moving rat. 247 Sep 97

Endothelin-1 (ET-1), a 21 amino acid peptide, has recently been identified and shown to produce a potent and prolonged constriction of mammalian blood vessels in vitro. We have studied the effect of local infusion of this peptide on resistance vessels in the hindlimb of the anesthetized greyhound dog. Incremental doses of ET-1 (3-200 pmol/min) were infused into the left femoral artery. Doses above 10 pmol/min produced a slowly progressive reduction in hindlimb blood flow in a dose dependent fashion, maximally reducing flow by 79.5% +/- 3.2 from 152.3 +/- 29.1 ml/min to 27.8 +/- 5.8 ml/min (+/- SEM, p less than 0.015), with a concomitant rise in vascular resistance. In the control vessel (right femoral artery) there were no statistically significant changes in blood flow observed. Onset time of the response to ET-1 was 3 min, whereas spontaneous recovery of the flow occurred at 30 min following cessation of the infusion. We demonstrated transient reversal of constriction in this arterial model during coinfusion with endothelin-1 (100 pmol/min) of dihydropyridine calcium channel blocking agent nicardipine (0.5-20 nmol/min), substance P (0.5-50 fmol/min), adenosine (10-10,000 pmol/min), and isosorbide dinitrate (0.001-0.1 mg/min).
J Cardiovasc Pharmacol 1989
PMID:Endothelin-1 is a potent long-lasting vasoconstrictor in dog peripheral vasculature in vivo. 247 15

The effect of endothelin-1 (ET-1) was investigated in the isolated spinal cord of the newborn rat. Bath-applied ET-1 produced a depolarization of a lumbar ventral root, which was suppressed by nicardipine or a substance P antagonist (spantide). In addition, the slow ventral root depolarization from L4 segment evoked by electrical stimulation of the contralateral sciatic nerve was also suppressed by spantide or nicardipine. However, nicardipine did not affect the ventral root depolarization induced by substance P, itself. These results indicate that the dihydropyridine-sensitive Ca2+ channels are associated with substance P release and that the effect of endothelin is probably mediated by substance P.
J Cardiovasc Pharmacol 1989
PMID:Endothelin-1 depolarizes a ventral root potential in the newborn rat spinal cord. 247 17

We have previously shown that porcine endothelin (ET-1) releases endothelium-derived relaxing factor (EDRF) in the rat isolated perfused mesentery. Here we show that both ET-1 (1-100 pmol) and rat endothelin (ET-3, 1-300 pmol) release EDRF in this preparation and that ET-1 releases EDRF from the luminally perfused aorta of the rabbit. Furthermore, we confirm that, as a pressor agent, ET-1 is greater than 10 times more potent than ET-3. Vasodilatations in the rat isolated perfused mesentery in response to ET-1 and ET-3 were due to the release of EDRF since they were inhibited by removal of the endothelium, methylene blue (100 microM), or hemoglobin (30 microM). ET-3 was more selective than ET-1 as a vasodilator because ET-1 induced vasodilatations were limited and in the higher doses overwhelmed by concurrent vasoconstrictions. Release of EDRF from the rabbit aorta in response to ET-1 but not to other agonists (acetylcholine, substance P, or adenosine diphosphate) was potentiated by infusion of potassium chloride (3 mM). Bay K 8644 failed to release EDRF in either system or to constrict the nondepolarized rat mesentery. Thus, both ET-1 and ET-3 release EDRF by activation of receptors or channels that differ from dihydropyridine-sensitive calcium channels.
J Cardiovasc Pharmacol 1989
PMID:Endothelin-1 and endothelin-3 release EDRF from isolated perfused arterial vessels of the rat and rabbit. 247 35

The therapeutic inhibition of angiotensin converting enzyme (ACE) is associated with the production of a dry cough, which occurs more commonly in women than men and appears to be unrelated to concurrent illness. At present the exact incidence of ACE inhibitor cough and the substrate of ACE responsible for this effect is unknown. Cough challenge by inhalation of aerosols of tussive agents such as citric acid and capsaicin may be used to study the effect of drug administration on the cough reflex. In normal subjects, an oral dose of captopril (25 mg) causes a significant shift in the dose-response curve to capsaicin inhalation, but not that to distilled water or citric acid. The exacerbation of artificially induced cough by ACE inhibition may be the result of a local increase in perineuronal substance P or bradykinin concentrations within the lung.
J Cardiovasc Pharmacol 1989
PMID:Cough associated with angiotensin converting enzyme inhibition. 247 6

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
Cardiovasc Res 1989 Sep
PMID:Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries. 248 33

In canine and porcine coronary arteries, experimental atherosclerosis (induced by endothelial denudation followed by a high-cholesterol diet) potentiates the vasoconstrictor effects of histamine, serotonin, and ergonovine. In isolated human atherosclerotic coronary arteries, only hypersensitivity to histamine has been demonstrated. This discrepancy could be due to several factors. First, the atherosclerotic lesions in human vessels are different from those observed in the animal, since experimental atherosclerosis often corresponds only to the early stage of the disease in humans. Second, the human atherosclerotic coronary arteries were isolated mainly from patients with cardiac failure, a condition that alters the responses of coronary smooth muscle to vasoactive amines. With regard to endothelium-dependent vasodilators, marked attenuations of the relaxations to substance P, bradykinin, and the Ca2+ ionophore A23187 have been described in isolated human atherosclerotic arteries. Acetylcholine elicits variable responses in these preparations and even if the arteries are devoid of atherosclerotic lesions, it often fails to relax them. In addition to this endothelial dysfunction, severely atherosclerotic human coronary vessels exhibit a slightly decreased responsiveness to nitroglycerin and SIN-1 but not to forskolin. Another abnormality of the smooth muscle is a marked attenuated beta-adrenergic relaxation. Thus, atherosclerosis of human coronary vessels induces not only marked alterations in endothelium-dependent responses but also modifies the sensitivity to several endothelium-independent vasodilators.
J Cardiovasc Pharmacol 1989
PMID:Atherosclerosis and responses of human isolated coronary arteries to endothelium-dependent and -independent vasodilators. 248 97

Human epicardial coronary arteries were obtained from the hearts of 15 patients who received cardiac transplantation for cardiomyopathy. Transverse strips of these arteries were mounted in organ baths for isometric tension recording. The arteries were constricted with prostaglandin F2 alpha and then exposed to the endothelium-dependent relaxants substance P (1 nM), bradykinin (1 nM-1 microM), and the Ca2+ ionophore A23187 (1 nM-1 microM). The effects of the endothelium-independent relaxants glyceryl trinitrate (1 nM-10 microM) and SIN-1, the active metabolite of molsidomine (1 nM-10 microM), were also tested. In control strips of human coronary arteries, all vasodilators caused concentration-dependent relaxations. Pretreatment of human coronary arteries with glyceryl trinitrate (0.5 mM for 60 min) shifted the concentration-response curve to glyceryl trinitrate to the right by a factor of approximately 800 (increase in EC50 from 10 nM to 8 microM). In contrast, endothelium-dependent relaxations to substance P, bradykinin, and A23187 and relaxations to SIN-1 were not changed significantly. Previous exposure of human coronary arteries to SIN-1 (0.5 mM for 60 min) did not modify relaxations to any of the agents tested. Our results show that (a) the responsiveness to SIN-1 is not modified in nitrate-tolerant strips of human coronary arteries, (b) prolonged exposure of human coronary arteries to SIN-1 does not cause tolerance, and (c) endothelium-dependent relaxations are not influenced by exposure of human coronary arteries to either glyceryl trinitrate or SIN-1.
J Cardiovasc Pharmacol 1989
PMID:Endothelium-dependent vasodilatation in human epicardial coronary arteries: effect of prolonged exposure to glyceryl trinitrate or SIN-1. 248 99


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