摘要:

Administration of adenosine results in profound hypotension without the expected activation of reflex sympathetic and renin mechanisms in most animal models. This action can be explained by the vasodilatory and neuroinhibitory effects of adenosine. It is generally considered an inhibitory neuromodulator because it inhibits the release of virtually all neurotransmitters studied and produces hyperpolarization of neurons. In contrast, adenosine produces vasoconstriction of some vascular beds, including the renal and pulmonary circulations. Renal vasoconstriction is caused by activation of A1receptors and involves an interaction with angiotensin EL In other vascular beds adenosine releases eicosanoids, including thromboxane, also resulting in vasoconstriction. Adenosine-induced vasoconstriction is transient and species dependent Neither the receptor type, the molecular mechanisms of these actions, nor their significance to pathophysiological processes have been defined. Adenosine also has an apparent excitatory effect in the nucleus tractus solitarii. Microinjections of adenosine into this brain stem nucleus lead to decreased sympathetic tone and hypotension similar to those produced by the excitatory amino acid glutamate. The mechanism that explains this action has recently been explored and involves the release of glutamate by adenosine. Adenosine also stimulates afferent fibers mediating sympathetic activity, including renal and myocardial afferent nerves, and carotid and aortic chemoreceptors. Afferent nerve activation seems to be more pronounced in humans and may explain most of the cardiovascular and respiratory actions of adenosine in this species. Finally, animal studies suggest that endogenous adenosine plays a role in the regulation of the baroreceptor reflex and restrains the full expression of renindependent hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To clarify the role of the renal and hypothalamic noradrenergic systems in the antihypertensive actions of dietary potassium supplementation in salt-loaded spontaneously hypertensive rats (SHR), we measured systolic blood pressure and noreplnephrine turnover, which was determined from the rate of decline of tissue norepinephrine concentration after the administration of α-methyl-p-tyrosine, in 5-week-old SHR or age-matched Wistar-Kyoto (WKY) rats eating normal-NaCl (0.66%) or high-NaCl (8%) diet with supplementation of 8% KCl. In WKY rats, neither high-sodium nor high-potassium diets had an effect on blood pressure with no change in renal or hypothalamic norepinephrine turnover. In SHR, however, salt loading accelerated the development of hypertension. Potassium supplementation did not affect blood pressure in normal-sodium SHR bat attenuated the rise in blood pressure with salt loads. Correspondingly, renal norepinephrine turnover in SHR was increased compared with that of WKY rats, and salt loading further potentiated the increased turnover in the kidney; however, no changes in hypothalamic turnover occurred. Potassium supplementation attenuated the rise in blood pressure with salt loads and the increased renal turnover. Stimulation of sympathetic discharge by cold exposure after the administration of α-methyi-p-tyrosine produced marked depletion of norepinephrine in most tissues. The loss of norepinephrine was significantly greater in both kidney and hypothalamus of salt-loaded SHR than in those of normal-sodium SHR, but potassium could normalize this. Thus, potassium not only diminished the increased renal norepinephrine turnover in the kidney under normal conditions but also attenuated the augmented renal and hypothalamic norepinephrine turnover by cold stress in salt-loaded SHR. The data suggest that hypothalamorenal noradrenergic systems might be involved in the hypotensive action of potassium in salt-loaded SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The effects of trandolapril (0.25 mg/kg body wt per 48 hours) on aortic atherosclerosis were examined in the Watanabe heritable hyperlipidemic rabbit treated from 3 to 12 months of age. Trandolapril caused a significant decrease in atherosclerotic involvement of the intimal surface of total aorta from 56.3 ±5.0% in control Watanabe rabbits to 35.0±4.1% with treatment (p<0.01). The largest redactions were observed in descending thoracic aorta where 21.8±5.7% of intimal surface was involved in the trandolapril-treated animals versos 54.4±7.7% in the control group (p<0.01). Significant decreases also occurred in ascending aorta/arch and abdominal aortic segments. Cholesterol content of descending thoracic aorta was also significantly reduced in the trandolapril-treated rabbits. The atherosclerotic plaques in aorta from trandolapril-treated rabbits appeared to contain less foam cells and relatively greater amounts of connective tissue than those from control animals. These studies indicate that trandolapril inhibits aortic atherosclerosis in the Watanabe heritable hyperlipidemic rabbit The similarity in results between the current study and that using captopril suggests that the antiatherosclerotic action of trandolapril and captopril represents a class effect related to angiotensin converting enzyme inhibition.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We investigated the preventive effects of long-term treatment with the angiotensin converting enzyme inhibitor ramipril on myocardial left ventricular hypertrophy and capillary length density in spontaneously hypertensive rats. Rats were treated in utero and subsequently up to 20 weeks of age with a high dose (1 mg/kg per day) or with a low dose (0.01 mg/kg per day) of ramipril. Animals given a high dose of ramipril remained normotensive, whereas those given a low dose developed hypertension in parallel to vehicle-treated controls. At the end of the treatment period, converting enzyme activity in heart tissue was inhibited dose–dependently in the treated groups. Both groups revealed an increase in myocardial capillary length density together with increased myocardial glycogen and reduced citric acid concentrations. Left ventricular mass was reduced only in high dose– but not in low dose–treated animals. Our results demonstrate that early onset treatment with a converting enzyme inhibitor can induce myocardial capillary proliferation, even at doses too low to antagonize the development of hypertension or left ventricular hypertrophy. We hypothesize that potentiation of kinins is responsible for this effect, probably by augmenting myocardial blood flow, which is a well-known trigger mechanism of angjogenesis in the heart.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

To determine whether expression of the renin-angiotensin system (RAS) is influenced by the degree of renal ablation, male Spragoe-Dawiey rats underwent nninephrectomy, 1 1/3 nepfarectomy, or sham operation. Renin and angiotensinogen messenger RNA (mRNA) were not different among the three groups 2 weeks after surgery. The time course of expression of renin mRNA after 1 1/3 nephrectomy showed no difference versus controls at 2 and 4 weeks and a decrease at 6 weeks after surgical ablation. Because nephrons adjacent to the infarcted area in the 1 1/3 nephrectomy may be hypoperfused and a source of increased renin synthesis, intrarenal distribution of tissue renin content, renin mRNA, and immunostainable renin were examined in separate groups of rats subjected to 1 1/3 nephrectomy. The kidney was divided into two pieces, one containing the scar and scar-adjacent tissue and the other portion the tissue distant from the scar. Tissue renin content, renin mRNA, and immnnostainable renin were significantly greater in the scar-adjacent tissue compared with the nonscar tissue. Immunoreactive renin was seen in the juxtaglomerular apparatuses as well as in vascular elements proximal to the juxtaglomerular apparatus and within mesangial cells of some glomeruli of the scar-adjacent tissue. In conclusion, immunostainable renin, tissue renin content, and renin mRNA were increased in scar-adjacent tissue after 1VS nephrectomy. We speculate that this unique scar-associated redistribution of renin may play a pathophysiological role in the progression of renal disease.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The aim of this study was to clarify how collagen deposition or medial hypertrophy of the vascular wall affects the coronary dilator reserve in pressure-overloaded hearts and whether inhibition of collagen deposition reverses the abnormalities after relief of pressure overload. We used ascending aortic banding and debanding methods and superimposed β-amlnopropionitrile in some of the banded rats (50 mg/kg i.p., twice a day). Ten weeks of banding increased in vivo peak systolic left ventricular pressure and produced medial hypertrophy, an increase in collagen deposition in the myocardial and pertvascular tissues, and myocardial hypertrophy in the banded group without β-aminopropionltrile treatment Superimposition of β-aminopropionitrile treatment on banding inhibited the increase in collagen deposition. In the groups debanded after the 10-week banding period, both with and without β-amlnopropionitrile treatment, medial and myocardial hypertrophy regressed 4 weeks after debanding. We estimated coronary dilator reserve in Langendorff preparations perfused with modified Tyrode's solution containing oxygenated bovine red blood cells and serum albumin. The ratio of reactive peak flow after brief ischemia-to-resting flow decreased in both of the banded groups. After debanding, the ratio remained lower in the banded group without β-aminopropionitrile treatment than in the control group. However, debanding in the group with β-aminopropionitrile treatment increased the ratio to a level similar to that of the control group. Thus, in pressure-overloaded cardiac hypertrophy with coronary hypertension, coronary reserve seems to be determined by medial hypertrophy independently of collagen deposition, but collagen deposition plays an important role in the reversal of vasodilator reserve after relief of the overload.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

Not only blood pressure but also behavioral activity, brain morphology, and cerebral ventricular size differ between young spontaneously hypertensive rats (SHR) and nonnotensive Wistar-Kyoto (WKY) rats. This suggests that cerebral blood flow and cerebral metabolism may vary between these two rat strains. To test this hypothesis, we measured local cerebral glucose utilization in 31 brain areas of 26–30 -week-old rats. Local cerebral blood flow was also assessed in these same areas. Cerebral glucose utilization was measured by the 2-deoxyglucose method; cerebral blood flow was determined by the iodoantipyrene method. In virtually all gray matter structures, the apparent rate of glucose utilization was lower in SHR than in nonnotensive WKY rats; the interstrain differences varied significantly among structures and were statistically significant (uncorrectedttests) in 14 of 28 gray matter areas. Local cerebral blood flow was fairly similar in the two rat strains. The coupling of blood flow to glucose utilization varied significantly among brain areas in nonnotensive WKY rats as well as in SHR. In a number of gray matter structures, the coupling of flow to metabolism differed between hypertensive and nonnotensive animals. These data suggest that for many brain areas, either glucose utilization or glucose partitioning differs between WKY rats and SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

This study was designed to Investigate the effects of L-arginine (the substrate of endothelium-derived nitric oxide) in human forearm vessels. We examined whether intra-arterial infusion of L-arginine dilated forearm vessels and augmented vasodilatory responses to acetylcholine in young, healthy humans. The left brachial artery was cannulated for drug infusions and direct measurement of arterial pressure. Forearm blood flow was measured by a strain gauge plethysmograph. Intra-arterial infusions of L-arginine at 10, 20, 40, and 60 mg/min increased forearm blood flow from 4.7±0.6 to 4.9±0.5, 5.7±0.5, 7.2±0.8, and 8.2±0.9 ml · min−1· 100 ml−1, respectively (n=8,p<0.01), whereas D-arginine at the same doses did not alter forearm blood flow (n=7). Intra-arterial infusions of acetylcholine (n=7) (4, 8,16, and 24 μg/min) and sodium nltroprusside (n=5) (0.2, 0.4, 0.8, and 1.2 μg/mln) increased forearm blood flow dose dependently (p<0.01 for both). Arterial pressure was not altered with infusions of these drugs. Responses to acetylcholine were augmented with simultaneous intra-arterial infusion of L-arginine at 10 mg/ml (p<0.01) but not with D-arginine. Responses to sodium nitroprusside were not altered by L-arginine. These results in human forearm resistance vessels support the notion that vasodilation induced by acetylcholine is a result of the conversion from L-arginine to endothelium-derived nitric oxide. Our results suggest that intra-arterial infusion of L-arginine may facilitate production of nitric oxide in the forearm and that L-arginine contributes to the modulation of vascular smooth muscle tone in healthy humans.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

The enzymatic conversion of human big endothelins (1, 2, and 3) to their respective active metabolites (endothelin-1, −2, and −3) was investigated in the perfused rabbit kidney through the pressor- and eicosanoid-releasing properties of these peptides. Intra-arterial bolus injections of endothelin-1 and −2 (5–50 pmol), endothelin-3 (100–250 pmol), and big endothelin-1 and −2 (100–250 pmol) into the kidney produced dose-dependent increases of perfuslon pressure, whereas big endothelin-3 was inactive at doses up to 1,000 pmol. Endothelin-1 and −2 (10 nM), endothelin-3 (100 nM), and big endothelin-1 and −2 (100 nM) are potent enhancers of prostacyclin release without inducing any release of thromboxane B2in the perfused kidney. In contrast, big endothelin-3 did not trigger the release of eicosanoids. A metalloprotease inhibitor, phosphoramidon (100 μM, 60 minutes), reduced the prostanoid release and pressor responses induced by big endothelin-1 and −2 without affecting the response induced by endothelin-1, −2, and −3. These results suggest the presence of a phosphoramidon-sensitive endothelin converting enzyme that converts the precursors of endothelin-1 and −2, but not of endothelin-3, in the renal vasculature of the rabbit.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID

摘要:

We have previously shown that renal vascular resistance is less in Dahl salt-sensitive rats than salt-resistant rats fed 1% NaCl diets; however, renal vascular resistance increases before nonrenal vascular resistance as salt-sensitive rats develop hypertension when fed 8% NaCl diets. When saltresistant rats are given 8% NaCl diets, renal vascular resistance decreases. The current study reports effects of atrial natriuretic peptide, nitroprusside, norepinephrine, angiotensin II, and endothelin-1 on renal and nonrenal vascular resistance in prehypertensive salt-sensitive and salt-resistant rats given 1% NaCl diets; doses used did not affect blood pressure. Resistance of nonrenal vessels in salt-sensitive and salt-resistant rats responded similarly to dilators or constrictors. However, atrial natriuretic peptide and nitroprusside decreased renal vascular resistance of salt-resistant rats (by 65%,p< 0.01) but not that of salt-sensitive rats. Noreplnephrine, angiotensin H, and endothelin-1 increased renal vascular resistance in salt-sensitive rats by 126%, 135%, and 135%, respectively (p<0.01); norepinephrine and angiotensin II did not change renal vascular resistance of salt-resistant rats, but endothelin-1 decreased renal vascular resistance in salt-resistant rats by 30% (p<0.01). Reactivity of nonrenal blood vessels in prehypertensive salt-sensitive and salt-resistant rats was similar when infused with dilators or constrictors in doses used. By contrast, renal vessels of salt-sensitive rats did not dilate in response to atrial natriuretic peptide and nitroprusside but were hypersensitive to norepinephrine and angiotensin II. Endothelin-1 caused renal vasoconstriction in salt-sensitive rats and renal vasodilation in salt-resistant rats. Inappropriate renal vascular reactivity in prehypertensive salt-sensitive rats may play an important role in salt-induced hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1992

数据来源: OVID