摘要:

Purified human α-thrombin induced a sustained contraction of isolated rabbit aorta and dog coronary arteries. These vascular tissues also exhibited a refractoriness towards a second thrombin exposure. The extent of tachyphylaxis exhibited by the aorta correlated with the initial concentration of thrombin and the length of time the tissue was exposed to thrombin. The thrombin-induced contraction in the aorta was not blocked by phospholipase or cyclooxygenase inhibitors, but it was inhibited in the presence of hirudin, heparin, nitroglycerin, and nitroprusside. Nitroglycerin, nitroprusside, and hirudin also inhibited the contraction in the dog coronary artery. Ca++ channel blockers did not inhibit the thrombin-induced contraction in the coronary artery, although a small inhibition was observed in Ca++-free media. In both tissues, equivalent contractile responses were obtained using equimolar quantities of β-, tetranitromethane-, and α-thrombin, even though the latter’s coagulant activity was 30-40 times that of the modified thrombins. However, if the catalytic activity of thrombin was inhibited by modification with Tos-Lys-CH2Cl, hirudin, or heparin/antithrombin III, the vasoconstrictor activity was also lost. These studies suggest that alterations of the fibrinogen-binding site do not affect the contractile activity of thrombin. The contraction may be the result of a proteolytic interaction of the active site of the enzyme with vascular smooth mu

ISSN:1018-1172    

DOI:10.1159/000158495

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

Ring segments of the rabbit ear artery were studied in the normal configuration (where drugs entered the media mainly through the adventitia) and in the everted configuration (where drugs entered mainly through the intima). Norepinephrine (NE) produced a faster response when added to the intima. This difference was not due to NE uptake mechanisms or asymmetry of different types of alpha-receptor. However, tetraethylammonium chloride (which abolishes rectification and increases membrane electrical activity) selectively increased the velocity of contraction of the normal artery segments to NE. These results suggest that approximately 50% of the difference between the intimal and adventitial velocity of contraction to NE is due to the presence of an intimal electromechanical coupling mechanism which does not operate at the adventitia. The remaining difference may be due to a closer proximity of medial alpha-receptor to the intimal surface.

ISSN:1018-1172    

DOI:10.1159/000158496

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The effect of modifications of the N-terminal end of the angiotensin II (AII) molecule on its ability to induce tachyphylaxis in the isolated rabbit aorta was studied by analyzing the effects of several analogs of AIL No tachyphylaxis to AII was observed, but (1-sarcosine)-AII, (1-guanido-acetic)-AII and (1-glycine)-AII induced marked tachyphylaxis. (1-Betaine)-AII, (2-lysine)-AII, (2-ornithine)-AII and (1-sarcosine,2-lysine)-AII were unable to induce tachyphylaxis in the rabbit aorta. A positively charged N terminus and the guanidino group of the Arg2 side chain appear to be needed for the manifestation of the tachyphylactic property, while the Asp1 side chain is responsible for the absence of tachyphylaxis to AII. It is proposed that the analogs that are able to induce tachyphylaxis, after binding to the receptor to produce the agonistic response, induce a slow conversion of the hormone-receptor complex into a tachyphylactic state, and that this conversion is promoted by the interaction of the N terminus and the guanidino group of the analog with their complementary sites.

ISSN:1018-1172    

DOI:10.1159/000158497

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The results of this study indicate that both cell proliferation and increased synthesis of extracellular matrix protein contribute to hypertrophy of the rat pulmonary trunk during the early development of hypoxia-induced pulmonary hypertension. As determined by autoradiography after 3H-thymidine injection, pulmonary hypertension results in increased labelling in all cell compartments of the pulmonary trunk wall, the most dramatic response occurring in the adventitia following 3 days’ hypoxic exposure. Autoradiography also demonstrated differences in the degree of incorporation of 3H-proline into extracellular protein between hypoxic (3 and 21 days) and control rats. The major focus of 3H-proline incorporation shifted from the adventitia at 3 days to the tunica media at 21 days, although incorporation was significantly higher at 3 compared to 21 days in all wall compartments. The patterns of hyperplasia and matrix protein synthesis in the extrapulmonary arteries of the rat, as reported here, are distinctly different from those seen in many large elastic arteries during development of systemic hypertension. For example, the hyperplastic response of arterial vessels follows a similar temporal sequence in pulmonary and systemic hypertension. However, the adventitia is the region of the pulmonary trunk with highest cell proliferation in pulmonary hypertension while the media is most affected by systemic hypertension. The relevance of the changing patterns of cell proliferation and protein synthesis in the wall of the pulmonary trunk of chronically hypoxic rats to the structural and biochemical properties of this vessel during the early development of pulmonary hypertension is discusse

ISSN:1018-1172    

DOI:10.1159/000158498

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

All nonelastin tissue was removed from canine aortas by placing them in 0.1 N NaOH at 75 °C for varying periods of time. The segments of aorta were weighed in a Mettler Chemical Balance at intervals. In 10 dogs the average weight of the thoracic aorta was 5.01 ± 0.388 (SE) g while that of the abdominal aorta was 3.08 ± 0.346 g. After digestion, the thoracic aorta weighed 3.34 ± 0.0275 g and the abdominal aorta 0.85 ± 0.085 g. Thus, the elastin makes up 67% of the thoracic aorta but only 28% of the abdominal aorta. These are equivalent to 0.334 g/kg body weight for the thoracic aorta and 0.224 g/kg body weight for the abdominal aorta. The values were always stable between 5 and 7 h and usually between 3 and 12 h. Aortic elastin was obtained from 5 dogs after 5-7 h of digestion and prepared for analysis by scanning electron microscopy. The dimensions of the fenestrations in the internal elastic laminae were quantified as described previously. The lower abdominal aorta had the largest holes (2.227 ± 0.048 µm), and the upper thoracic aorta the smallest holes (0.954 ± 0.032 µm). There was no significant difference in the size of the fenestrations along the thoracic aorta, but those in the lower abdominal aorta were larger than those in the upper abdominal aorta. The possible significance of the fenestrations in the genesis of aortic disease is discussed

ISSN:1018-1172    

DOI:10.1159/000158499

出版商:S. Karger AG    

年代:1984

数据来源: Karger

摘要:

The mode of the ATP-induced vasoconstriction in the internal carotid artery was studied from the physiological and pharmacological points of view. ATP caused dose-dependent vasoconstrictions in the canine internal carotid artery. The ATP-induced vasoconstriction was not affected by pretreatment with phenoxybenzamine, propranolol, atropine, cyproheptadine, or tetrodotoxin. Verapamil suppressed the contractile response. ATP produced no vasoconstriction in a calcium-free Krebs solution containing 1 mM EGTA nor augmentation of Ca2+-induced contraction in potassium-depolarized tissues. These results suggest that an increase of potential-dependent Ca2+ influx into the arterial smooth muscle may play a major role in the ATP-induced vasoconstriction.

ISSN:1018-1172    

DOI:10.1159/000158500

出版商:S. Karger AG    

年代:1984

数据来源: Karger