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)

The effects of coronary artery disease (CAD) on human coronary microvascular responses to vascular endothelial growth factor (VEGF) and the alterations of the myocardial expressions of VEGF and its flk-1 and flt-1 receptors were examined in 48 patients. Microvascular studies were performed in vitro with video microscopy. The expressions of VEGF and its receptors were examined using Northern analysis of total mRNA, and the expressions of constitutive nitric oxide synthase (cNOS) and inducible nitric oxide synthase (iNOS) were examined by RT-PCR. VEGF and hepatocyte growth factor (HGF) caused potent relaxations of microvessels. These responses were reduced in the presence of NG-nitro-L-arginine and the tyrosine kinase inhibitor genistein or in microvessels from patients with CAD. Relaxations to substance P and sodium nitroprusside were similar in both groups. The substance P response was abolished in the presence of NG-nitro-L-arginine. The expression of VEGF and its receptors and the expression of cNOS and iNOS were not altered in patients with CAD. In conclusion, VEGF and HGF elicit the release of nitric oxide through activation of tyrosine kinase receptors. CAD is associated with reduced vascular responses to both VEGF and HGF; this is not likely due to a reduced expression of VEGF or flt-1 or flk-1 receptors and not due to a generalized endothelium dysfunction despite the presence of mild hypercholesterolemia in these patients with CAD. These findings may have important implications regarding the efficacy of endogenous and exogenous VEGF in patients with risk factor for CAD.
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PMID:Effects of coronary artery disease on expression and microvascular response to VEGF. 974 92

The extent to which reported abnormal responses of the human coronary circulation to acetylcholine in patients with hypercholesterolemia reflect endothelial injury is not clear. We used an in vitro rabbit model to determine whether these reactions involve endothelial or vascular smooth muscle dysfunction. Coronary resistance arterioles were isolated from hearts of rabbits fed 1% cholesterol to induce hypercholesterolemia or a control diet for 4 weeks. Arterioles were double cannulated with glass micropipettes and pressurized in a no-flow state. Acetylcholine contracted the arterioles in a concentration-dependent manner whether or not the nitric oxide synthase inhibitor N(G)-monomethyl-L-arginine was added. In control but not hypercholesterolemic preparations, contraction was significantly greater when endothelium was removed. In the hypercholesterolemic group, contraction significantly exceeded that in controls. In control but not high-cholesterol preparations, substance P dilated vessels with intact endothelium in a concentration-dependent manner. Addition of N(G)-monomethyl-L-arginine inhibited this response. With or without endothelium, norepinephrine contracted arterioles to a greater extent in the hypercholesterolemic group than in controls. We concluded that severe hypercholesterolemia decreased endothelially dependent factors by injuring endothelium and independently increased contractility of vascular smooth muscle.
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PMID:Acetylcholine-Induced response of coronary resistance arterioles in cholesterol-fed rabbits. 1059 72

Endothelium controls vascular smooth muscle tone by secreting relaxing and contracting factors. There is a constant release of endothelium derived relaxing factors, mainly nitric oxide, a potent vasodilator, inhibitor of platelet aggregation, monocyte adhesion and smooth muscle proliferation. In addition, the endothelium may increase the release of NO in response to humoral stimulation by vasoactive substances such as acetylcholine, bradykinin or substance P. Although the endothelium releases a number of products, no single blood test has yet proved useful to determine normal endothelial function or as early abnormalities. The most useful test of endothelial function relies on the measurement of endothelium-dependent dilatation in response to pharmacological or physiologic stimuli. The alteration of this response is known as endothelial dysfunction and has been observed in a variety of circumstances related to cardiovascular risk. This review summarizes the evidence that sustains this association and emphasizes the clinical utility of assessing endothelial function presenting two clinical cases of hypercholesterolemia in which a high-resolution vascular ultrasound in the brachial artery was used.
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PMID:[Endothelial dysfunction as a primary disorder in vascular diseases]. 1101 67

Recent evidence suggests that some benefit from the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors may occur independent of lipid lowering. We aimed to determine the effect of simvastatin on coronary endothelial function, endothelial NO synthase (eNOS) expression, and oxidative stress in experimental hypercholesterolemia (HC) in the absence of cholesterol lowering. Pigs were randomized to 3 experimental groups: normal diet (N group), high cholesterol diet (HC group), and HC diet with simvastatin (HC+S group) for 12 weeks. Low density lipoprotein cholesterol was similarly increased in the HC and HC+S groups compared with the N group. In vitro analysis of coronary large- and small-vessel endothelium-dependent vasorelaxation was performed. The mean vasorelaxation of epicardial vessels to bradykinin was significantly attenuated in the HC group compared with the N group (32.3+/-1.2% versus 42.9+/-1.6%, respectively; P<0.0001). This attenuation was significantly reversed in the HC+S group (38.7+/-1.5%, P<0.005 versus HC group). The maximal vasorelaxation to substance P was significantly attenuated in the HC group compared with the N group (50.5+/-11.9% versus 79.3+/-5.3%, respectively; P<0.05). This attenuated response was normalized in the HC+S group (74.9+/-4.1%, P<0.05 versus HC group). The maximal arteriolar vasorelaxation to bradykinin was also significantly attenuated in the HC group compared with the N group (71.9+/-4.9% versus 96.8+/-1.34%, respectively; P<0.005). This was reversed in the HC+S group (98.4+/-0.6%, P<0.0001 versus HC group). Western blotting of coronary tissue homogenates for eNOS demonstrated a decrease in protein levels in the HC group compared with the N group, with normalization in the HC+S group. Elevation of plasma F(2)-isoprostanes and thiobarbituric acid-reactive substances, markers of oxidative stress, occurred in the HC compared with the N group. These changes were reversed in the HC+S group. In summary, simvastatin preserves endothelial function in coronary epicardial vessels and arterioles in experimental HC (in the absence of cholesterol lowering) in association with an increase in coronary eNOS levels and a decrease in oxidative stress. These alterations may play a role in the reduction in cardiac events after treatment with 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors.
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PMID:Simvastatin preserves coronary endothelial function in hypercholesterolemia in the absence of lipid lowering. 1114 43

Capsaicin, the pungent alkaloid of red pepper (Capsicum annuum) has been extensively studied for its biological effects which are of pharmacological relevance. These include: cardio protective influence, antilithogenic effect, antiinflammatory, and analgesia, thermogenic influence, and beneficial effects on gastrointestinal system. Therefore, capsaicinoids may have the potential clinical value for pain relief, cancer prevention and weight loss. It has been shown that capsaicinoids are potential agonists of capsaicin receptor (TRPV1). They could exert the effects not only through the receptor-dependent pathway but also through the receptor-independent one. The involvement of neuropeptide Substance P, serotonin, and somatostatin in the pharmacological actions of capsaicin has been extensively investigated. Topical application of capsaicin is proved to alleviate pain in arthritis, postoperative neuralgia, diabetic neuropathy, psoriasis, etc. Toxicological studies on capsaicin administered by different routes are documented. Capsaicin inhibits acid secretion, stimulates alkali and mucus secretion and particularly gastric mucosal blood flow which helps in prevention and healing of gastric ulcers. Antioxidant and antiinflammatory properties of capsaicin are established in a number of studies. Chemopreventive potential of capsaicin is evidenced in cell line studies. The health beneficial hypocholesterolemic influence of capsaicin besides being cardio protective has other implications, viz., prevention of cholesterol gallstones and protection of the structural integrity of erythrocytes under conditions of hypercholesterolemia. Beneficial influences of capsaicin on gastrointestinal system include digestive stimulant action and modulation of intestinal ultrastructure so as to enhance permeability to micronutrients.
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PMID:Biological Activities of Red Pepper (Capsicum annuum) and Its Pungent Principle Capsaicin: A Review. 2567 68


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