ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Studies were undertaken to determine the mechanisms leading to altered mitochondrial function in ischemic myocardium. A new procedure has been developed to routinely isolate 60-70% of the total mitochondrial protein from heart tissue. After 1 hour of ischemia, mitochondria exhibit decreases of more than 50% in phosphorylating respiration for both NADH-and succinate-linked substrates compared to controls. However, no significant decreases in the efficiency of mitochondrial ATP synthesis (ADP:0) or ATPase activity are observed. Rates of substrate-driven Ca2+uptake exhibit decreases greater than that seen with phosphorylating respiration with incomplete uptake and pre-mature release of Ca2+. Spectrophotometric measurements in ischemic heart reveal rapid oxidation or loss of mitochondrial NADH with marked "swelling" of the inner membrane compartment; both changes parallel the loss of Ca2+. Significant losses in intramitochondrial adenine nucleotides also are found. Mitochondrial retention of accumulated Ca2+can be restored by addition of small amounts of exogenous adenine nucleotides (ATP or ADP) with concomitant attenuation of both NADH oxidation and "swelling." The data indicate that, following 1 hour of ischemia, the effeciency of mitochondrial ATP production is still relatively intact whereas both electron transport chain activity and calcium transport are severely compromised. These decreases appear to be related to selective membrane damage in the mitochondrial inner membrane.Circ Res 47: 814-820, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Baroreceptor resetting during hypertension has been attributed to a reduction in the distensibility of the vessel wall in which the receptors are located. According to this hypothesis, a simple increase in pressure is all that is required to overcome the increase in vessel wall stiffness. However, previous work from our laboratory suggested a more complicated situation. Measurements of both vessel wall mechanical properties and baroreceptor discharge characteristics in spontaneously hypertensive rats (SHR) showed that distortion thresholds for the receptors also undergo changes. Here we have examined the time course of resetting, measuring both aortic distensibility and barore-ceptor properties in SHR and mormotensive Wistar-Kyoto rats (WKY) from 5 to 30 weeks in age. An in vitro aortic arch-aortic nerve preparation was used. We found that for a given pressure the aortic radii of WKY were increasing much more rapidly than the aortic radii for SHR and, beyond 5 weeks of age, were much more distensible. The lower distensibility in SHR was accompanied by increased wall thickness. The discharge characteristics of single baroreceptors were expressed in terms of both pressure and distortion or circumferential wall strain. The change in distensibility of WKY aortas from 5 to 30 weeks was suitably matched by an increase in the strain threshold for discharge of WKY baroreceptors resulting in a constant pressure threshold for discharge. The lower distensibility of SHR aortas was accompanied by lower threshold strains in SHR baroreceptors, but the changes were not suitably matched, and progressive resetting of SHR baroreceptors to higher threshold pressures occurred. The two sets of receptors appear to be different as early as 5 weeks of age when blood pressures are similar and, futhermore, these differences are accentuated by age and hypertension.CircRes 47: 821-828, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

In the previous paper we showed that baroreceptor resetting in spontaneously hyperten-sive rats (SHR) resulted from an incomplete matching of increased receptor strain sensitivity with reduced vessel wall distensibility. Here SHR and Wistar-Kyoto controls were treated with antihyper-tensive drugs in their drinking water (reserpine, hydrochlorothiazide, and hydralazine) from 5 weeks of age so that we might examine the role of blood pressure in the SHR vessel wall-receptor mismatch. Radius and receptor properties were measured using the in vitro aortic arch-aortic nerve preparation at 8, 14, 20, and 30 weeks. We found that baroreceptors from SHR with normal blood pressures had normal pressure thresholds and suprathreshold pressure sensitivities. However, the treated SHR receptors still had lower strain thresholds and the aortas still were less distensible than were the normal. Now, however, the increased receptor sensitivity was sufficient to normalize the relationship between baroreceptor function and arterial blood pressure. We conclude that, although blood pressure may be restored to normotensive levels by therapy, vascular abnormalities may continue to develop.CircRes 47: 829-834, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Isoproterenol infusion (0.1 μ/kg per min) into the renal artery of the cat induced an increase in plasma renin concentration (PRC) from 14.3 ± 5.7 (mean ± SE) ng angiotensin I/ml per hr to 56.8 ± 7.7 after 70 minutes{P <0.05) and an increase in catecholamine secretion rate from 38.7 ± 6.0 ng/kg per 10 min to 180.0 ± 40.0 after 70 minutes(P< 0.001). Intravenous infusion of the same dose of isoproterenol had no significant effect on adrenomedullary catecholamine secretion rate. Isoproterenol induced preferential norepinephrine release: the ratio of norepinephrine to epinephrine secretion changed from 11.5:23.7 during the control period to 130.0:40.1 70 minutes after the start of isoproterenol administration. Intrarenal infusion of propranolol (3.0 mg/kg per min) inhibited renal renin release and adrenal catecholamine secretion in response to intrarenal isoproterenol. Intravenous infusion (0.4 Mg/kg P e r m in) °fan angiotensin II antagonist [Sar Ileu8]angiotensin II abolished the catecholamine response to intrarenal isoproterenol infusion. It is suggested that intrarenal isoproterenol infusion stimulates renal renin release and angiotensin production which, in turn, stimulates a preferential secretion of adrenomedullary norepinephrine.Circ Res 47: 835-839, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

In contrast to most renal vasodilators, such as acetylcholine (ACh), secretin increases renal blood flow in the dog without a marked effect on sodium excretion (UNaV). To investigate this observation, we studied the relationship between renal vasodilation, UNa»V, and papillary plasma flow (PPF) in rats, infused either with ACh or secretin into the aorta at the level of both renal arteries. ACh significantly increased GFR, PAH clearance, and UNaV (Δ + 0.35 ml/min, + 2.11 ml/min and + 1.77 /iEq/min, respectively;P< 0.05). PPF rose from 50 ± 2.6 ml/min 100 g (mean ± SE) in control rats to 91 ± 4.7 ml/min 100 g after ACh (P< 0.001). Despite a similar increase in PAH clearance after secretin (+ 2.21 ml/min; P< 0.01), UNaV remained unchanged and PPF was only slightly, although significantly, increased (from 50 ± 2.6 ml/min 100 g to 65 ± 2.75 ml/min 100 g;P< 0.05). Both total kidney and papillary vasodilation, and the increase in UNaV after ACh were blocked by previous administration of meclofenamate (M), a prostaglandin inhibitor. No effect of M in secretin-infused rats was observed. In conclusion, the relationship between total renal vasodilation and natriuresis was dissociated with secretin, but not with ACh. However, a relationship between the natriuresis and influence on papillary hemodynamics was observed with both vasodilators. Finally, the renal hemodynamic and natriuretic effects of ACh are probably mediated by prostaglandin release.Circ Res 47: 839-844, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We performed experiments to determine the effects of acetylstrophanthidin (ACS) and ouabain on the adrenergic neuroeffector junction in dog saphenous veins. In quiescent strips incubated with3H-norepinephrine (3H-NE), the drugs caused contraction and a progressive increase in overflow of3H-NE and O-methylated metabolites; 3,4-dihydroxyphenylglycol (DOPEG) decreased. Tissue uptake of3H-NE was partially inhibited. After surgical sympathectomy, both contraction and3H-NE overflow were markedly attenuated. Following chemical sympathectomy with 6-hydroxydopamine, ouabain contractions were 11% of control, whereas the contractions due to exogenous norepinephrine were exaggerated. The initial overflow of3H-NE was unaffected by tetrodotoxin, but the later and larger overflow with prolonged exposure was depressed. The former occurred in the absence of Ca2+, but the latter was Ca2+dependent. Inhibition of the neuronal amine carrier by cocaine or desipramine and blockade of the neuronal a-adrenoceptors with phentolamine or phenoxybenzamine attenuated the release of3H-NE evoked by ACS and ouabain. During electrical stimulation, ACS augmented the overflow of3H-NE. This was attenuated by cocaine, desipramine, and the a-adrenolytic drugs. ACS, like pargyline, augmented the overflow of3H-NE evoked by tyramine and depressed that of DOPEG. These experiments suggest that acetylstrophanthidin and ouabain (1) cause contraction of vascular smooth muscle by displacement of norepinephrine from neuronal stores, (2) reduce neuronal mono-amine oxidase activity, (3) facilitate and may trigger Ca2+-dependent exocytotic release of norepineph-rine, (4) partially inhibit the neuronal amine carrier mechanism but do not interfere with extraneuronal disposition of norepinephrine, and, finally (5) may have unexplained interactions with prejunctional a-adrenoceptors.Circ Res 47: 845-854, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the interaction of disopyramide, quinidine, and procainamide with cardiac muscarinic receptors. In electrophysiological experiments, the effects of disopyramide, quinidine, procainamide, and atropine were determined on spontaneously depolarizing guinea pig right atria (GPRA) both in the presence and absence of pharmacologically induced (physostigmine) cholinergic stimulation. All four agents demonstrated a concentration-dependent antagonism of the negative chronotropic effects of physostigmine. The order of anticholinergic potency was atropine » disopyr-amide > quinidine » procainamide. The ability of disopyramide to antagonize the physostigmine induced slowing was stereoselective, (+)disopyramide > (—)disopyramide. In contrast, the ability of quinidine to antagonize the negative chronotropic effects of physostigmine was non-stereoselective, quinidine = quinine. In parallel experiments, we studied the ability of disopyramide, quinidine, procainamide, and atropine to compete with the radiolabeled muscarinic receptor antagonist [3H] quinuclidinyl benzilate ([3H]QNB) for binding to muscarinic receptors in crude homogenates of GPRA and membrane vesicles from canine ventricular myocardium. All four agents inhibited [3H]QNB binding to muscarinic receptors. The order of anticholinergic potency determined by the receptor binding studies was identical to that determined by the physiological studies. The interaction of disopyramide with muscarinic receptors was stereoselective, (+)disopyramide > (−)disopyramide. Quinidine was only slightly more potent than quinine in inhibiting [3H]QNB binding to muscarinic receptors. Inter-action of antiarrhythmic drugs with muscarinic receptors satisfied criteria for a competitive interaction. The data from this study localize the anticholinergic effects of disopyramide and quinidine to the muscarinic receptor.Circ Res 47: 855-865, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

We studied the effects of steady state increases in left atrial pressure on the albumin-excluded volume in the lungs of mongrel dogs. We estimated the tissue blood volume using51Cr-labeled red cells, the extracellular space using99mTc-DTPA (diethylene triamine pentacetic acid), and the albumin space using125I-labeled human serum albumin. An afferent lymphatic to the left tracheobron-chial node was cannulated for measurement of lymph flow, total protein and albumin concentration. Total extravascular water (Qw), extravascular "Tc-DTPA space, extravascular albumin content, and albumin space were calculated in lung tissue samples taken during a baseline period and during steady states, following increases in pulmonary capillary pressure. Lymph flow increased by 0.20-fold, and Qw by 0.05 g/g blood free dry weight for each cm H2O increase in capillary pressure over the range of capillary pressures used in this study. Using an extravascular albumin space based on the concentration of albumin in lymph, an excluded albumin volume of 36% of the extravascular99mTc-DTPA space was calculated for normally hydrated lungs. This excluded volume fraction decreased to approximatley 10% of the extravascular99Tc-DTPA space at capillary pressures above 30 cm H2O. Oncotic buffering increased the plasma to lymph colloid osmotic pressure gradient, and buffered approximately 29% of the increase in pulmonary capillary pressure. Excluded volume had a simple physicochemical relation-ship to tissue hydration. It also served as a "safety factor" against pulmonary edema because there was a greater increase in available volume than total interstitial volume during edema formation. Oncotic buffering then could occur with a smaller increase in interstitial fluid volume than would otherwise be possible.Circ Res 47: 866-875, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID

摘要:

Analysis of the relationships between cardiac oxygen usage (MVO2), cardiac muscle adenosine levels ([Ado]), and coronary vascular resistance (R) in open-chest, anesthetized dogs tested the hypothesis that adenosine is a physiological regulator of coronary flow. Experiments using each dog as its own control showed that [Ado] varied directly with MVO2 as the latter changed spontaneously or in response to atrial pacing, paired pacing, aortic constriction, or β-adrenergic blockade. In turn, R varied inversely with changes in [Ado]. Stimulating MVO2with isoproterenol significantly increased the slope of the regression of [Ado] on MVO2 as well as of R"1on [Ado]. The effect of β-adrenergic stimulation on [Ado] is unexplained, but its effect on R"1seems to reflect the combined effects of adenosine and direct β-adrenergic coronary relaxation. These results support the hypothesis that adenosine mediates the coronary flow responses to changes in MVO2.Circ Res 47: 875-882, 1980

ISSN:0009-7330    

出版商:OVID    

年代:1980

数据来源: OVID