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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As the major regulator of arterial blood pressure and sodium balance, the renin axis supports normotension or hypertension via angiotensin-mediated vasoconstriction and angiotensin plus aldosterone-induced renal sodium retention. In this endocrine servo control, renal renin is released by hypotension or salt depletion; conversely, with hypertension or volume excess, plasma renin activity falls to zero. Accordingly, any renal renin secretion is abnormal in the face of arterial hypertension. Human hypertensive disorders comprise a spectrum of abnormal vasoconstriction-volume products (renin-sodium profiles). Excess plasma renin activity for the sodium balance is created by nephron heterogeneity in which a subpopulation of ischemic nephrons hypersecretes renin and retains sodium. This excess renin impairs adaptive natriuresis of neighboring normal nephrons. Research defining the pivotal role of vascular cytosolic calcium for transducing sodium or renin-mediated vasoconstriction explains the selective value of calcium antagonists for correcting the sodium-volume-mediated, and beta-blockers or angiotensin converting enzyme inhibitors for correcting renin-mediated, arteriolar vasoconstriction. The renin precursor prorenin appears to be physiologically active, causing selective vasodilation that offsets renin-mediated vasoconstriction. Overactivity of prorenin may be involved in the hyperperfusion vascular injuries of diabetes mellitus and toxemias. Prorenin underactivity may facilitate renin-mediated ischemic vascular injury. In essential hypertension, undue plasma renin activity is powerfully and independently associated with heart attack risk. Conversely, patients with low renin activity are protected from heart attack despite higher blood pressures and greater age. Also, renin or angiotensin administration consistently causes vascular injury in the heart, brain, and kidneys of animals. These data suggest new potentials for the prevention of cardiovascular sequelae (heart attack and stroke) by using explicit strategies to curtail plasma renin activity.
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PMID:Lewis K. Dahl Memorial Lecture. The renin system and four lines fo hypertension research. Nephron heterogeneity, the calcium connection, the prorenin vasodilator limb, and plasma renin and heart attack. 151 45

The cardiovascular effects of 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitro phenyl) oxtyl ester (NP-252, CAS 132031-81-3) were examined in anesthetized closed- or open-chest dogs and Langendorff perfused rabbit hearts, and compared with those of nifedipine (NF) and nicardipine (NC). In anesthetized closed- and open-chest dogs, NP-252 (i.v.) selectively increased vertebral and coronary blood flow with a fall in mean blood pressure (MBP). These effects were nearly equipotent with those of NF and NC, but more durable. A similar effect was obtained by intraduodenal administration of NP-252. Also, NP-252 (i.v.) decreased MBP, total peripheral resistance (TPR), left ventricular pressure and dLVP/dtmax while cardiac output (CO) and stroke volume (SV) increased without apparent changes in heart rate and myocardial contractility index. Decreases in MBP and TPR by NP-252 were equipotent with NF and NC, whereas increases in CO and SV were more potent than those of the two drugs. These actions of NP-252 were longer than those of the reference agents. Further, in perfused rabbit hearts, NO-252 increased coronary perfusion flow (CPF), accompanying a slight negative inotropy. Its effect in CPF was equipotent with NF and 2 times less than that of NC, however the duration was much longer than those of the reference drugs. On the other hand, the negative inotropic effect of NP-252 was less than NF, but greater than that of NC. In the preparations controlled by pacing, NP-252 and NF lengthened atrio-His bundle conduction time, without affecting His bundle-ventricular conduction time. Lengthening effect of NP-252 was about 4 times less than that of NF. These results suggest that NP-252 acts more selectively on vascular smooth muscle than cardiac muscle, and has almost equipotent but markedly longer vasodilating actions as compared to NF and NC. It may be expected that NP-252 is a new generation of tissue specific and long acting Ca2+ antagonist.
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PMID:Cardiovascular effects of the new generation calcium antagonist 3-pyridine carboxylic acid 5-[(cyclopropylamino)carbonyl]-1,4-dihydro-2,6-dimethyl-4-(2-nitropheny l) octyl ester. 153 Jun 74

In muscle fibres labelled with iodoacetamidotetramethylrhodamine at Cys707 of the myosin heavy chain, the probes have been reported to change orientation when the fibre is activated, relaxed or put into rigor. In order to test whether these motions are indications of the cross-bridge power stroke, we monitored tension and linear dichroism of the probes in single glycerol-extracted fibres of rabbit psoas muscle during mechanical transients initiated by laser pulse photolysis of caged ATP and caged ADP. In rigor dichroism is negative, indicating average probe absorption dipole moments oriented more than 54.7 degrees away from the fibre axis. During activation from rigor induced by photoliberation of ATP from caged ATP in the presence of calcium, the dichroism reversed sign promptly (half-time 12.5 ms for 500 microM-ATP) upon release of ATP, but then changed only slightly during tension development 20 to 100 milliseconds later. During the onset of rigor following transfer of the fibre from an ATP-containing relaxing solution to a rigor medium lacking ATP, force generation preceded the change in dichroism. The dichroism change occurred slowly (half-time 47 s), because binding of ADP to sites within the muscle fibre limited its rate of diffusion out of the fibre. When ADP was introduced or removed, the dichroism transient was similar in time course and magnitude to that obtained after the introduction or removal of ATP. Neither adding nor removing ADP produced substantial changes in force. These results demonstrate that orientation of the rhodamine probes on the myosin head reflects mainly structural changes linked to nucleotide binding and release, rather than rotation of the cross-bridge during force generation.
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PMID:Transients in orientation of a fluorescent cross-bridge probe following photolysis of caged nucleotides in skeletal muscle fibres. 153 Sep 78

Maximum heart rates (HR) of three soricine shrews and six other small mammals were measured in response to a single supramaximal dose of isoproterenol (Iso) under urethan anesthesia. The highest HR, 1,043 +/- 66 (SD) beats/min (n = 3), was in least shrew (Sorex minutus, mean body mass 3.02 +/- 0.81 g). Maximum HRs of common shrew (Sorex araneus, 7.16 +/- 1.54 g) and water shrew (Neomys fodiens, 12.80 +/- 1.54 g) were 938 +/- 29 (n = 7) and 887 +/- 21 (n = 6), respectively. In general, maximum HRs of soricine shrews and other small wild mammals followed the common mammalian pattern, fHmax/Iso = 443 x Mb-0.14, determined by body size. The exponent for this equation is smaller than that of resting HR (-0.25) (Stahl, J. Appl. Physiol. 22: 453-460, 1967), predicting crossover at approximately 3 g body mass. However, resting HRs of small mammals were clearly lower than expected on the basis of body mass. Lowering resting HR below the common mammalian level, with concomitant increase in stroke volume, seems to be a prerequisite for small mammals to regulate cardiac output against the ceiling of maximum HR. Electrophoretic analysis showed that the myosin of shrew ventricles is different from those of rodent species. In native conditions, shrew myosin, designated V1', migrated faster than the V3 and V1 forms of rat heart. On SDS gradient gel the single heavy chain of shrew myosin migrated slower than the alpha- or beta-chains of rat ventricle. Differences in the molecular weight of light chains were also noted between small mammals. Despite the notable differences in myosin composition, myosin-ATPase activity of the shrew hearts was similar to that of mouse and rat heart. Because duration of isometric contraction was inversely related to resting and maximum HRs, it was concluded that in the small mammals rate and duration of contraction are determined mainly by the release and uptake rate of myoplasmic Ca2+ and less by myosin-ATPase activity.
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PMID:Maximum heart rate of soricine shrews: correlation with contractile properties and myosin composition. 153 6

In response to several agonists, tail arteries from spontaneously hypertensive stroke prone rats (SHRSP) contract in an oscillatory manner not observed in tail arteries from normotensive rats. This study evaluated whether oscillations in force development characterize the contractile pattern of vertebral arteries from hypertensive humans. Vertebral arteries were isolated and studied within 18-24 h post mortem. Helical strips of the arteries were mounted in a muscle bath for isometric force recording. Contractile responses to serotonin (10(-7)M) and endothelin (10(-8)M) in arteries from hypertensive subjects were characterized by fluctuations in force development whereas those in arteries from normotensive subjects usually remained constant with time. The frequency of the response was approximately 1-2 contraction/relaxation cycles per min. This pattern of oscillatory contractile activity was observed in all but one of the hypertensive arteries (n = 15), and in approximately 40% of the normotensive arteries (n = 12). Oscillatory activity was converted to maintained contraction by nifedipine (10(-7)M) which also caused relaxation of the contractile response. Relaxation to acetylcholine (10(-6)M) and nitroglycerin (10(-6)M) did not alter the oscillatory contractions. Endothelium removal did not influence the oscillatory pattern of contraction. These observations suggest that oscillatory contractile activity in vertebral arteries from hypertensive subjects is related to abnormal calcium entry into the smooth muscle cells. This altered membrane property may contribute to changes in vascular reactivity in hypertension.
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PMID:Oscillatory contractions in vertebral arteries from hypertensive subjects. 154 Oct 85

Nutrition has always been a subject of great interest to athletes. In recent years use of exercise has, however, expanded from competitive sports to prevention/management of chronic diseases and maintenance of optimal health. Exercise is recommended in the prevention/management of noninsulin-dependent diabetes, hypertension, coronary heart disease, osteoporosis, obesity, mental health, colon cancer, stroke and back injury. Similarly, there is evidence that certain nutrients (e.g., vitamins C and E, beta-carotene and calcium) may reduce the risk of certain cancers, coronary heart disease, osteoporosis, hypertension and cataract. Thus, there seems to be concordance between the health benefits of exercise and certain nutrients. However, several human and animal studies suggest that strenuous exercise may promote free radical production, leading to lipid peroxidation and tissue damage. On the other hand, there is evidence that vitamins C and E and beta-carotene may protect against such damage. Thus, concordance between the health benefits of exercise and nutrition and a compensatory role of antioxidant nutrients against the potentially harmful effects of exercise suggests that nutrition and exercise should form important components of any regimen for prevention of chronic diseases and/or promotion of optimal health.
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PMID:A current perspective on nutrition and exercise. 154 45

The four most popular classes of antihypertensive drugs may all be considered suitable choices when initiating treatment for hypertension. The practitioner must decide which agent is appropriate for each individual patient. The main goal of treatment should be to prevent coronary events and stroke, while preserving quality of life. A 40% reduction in stroke can probably be achieved with any antihypertensive treatment, a reduction in coronary events is much harder to achieve. Available evidence from studies in men, summarized in this review, indicates that beta-blockade is superior to thiazide diuretics for the prevention of coronary events. Clinical trials have not yet produced long-term prognostic data on the effects of ACE-inhibitors or calcium antagonists on coronary events in hypertensive patients. A recent review on calcium antagonists in post-MI patients concluded that the results were disappointing, as pooled data actually showed a trend towards increased mortality with calcium antagonists as compared with placebo. Because of the large number of hypertensive patients at increased risk for coronary events in the community, the difference observed in coronary events between beta-blockade and other first-line drugs in hypertension (24%) may have important implications for clinical practice. This overall conclusion, however, has to be accepted with some reservations in view of the following observations. Firstly, no reduction in sudden death has been observed with the hydrophilic beta-blockers. Secondly, no reduction in coronary mortality in the smoking subgroup has been observed with the non-selective beta-blockers. Thus, it seems that the prevention of coronary events is more likely to be observed in patients given beta-blockers with certain pharmacological characteristics: relative lipophilicity, which enables passage of the beta-blocker through the blood-brain barrier to exert effects on pertinent central nervous beta 1-receptors. This is potentially useful in reducing the risk of sudden death. The addition of beta 1-selectivity is important for the risk reduction in smokers. Cardioselectivity is also an advantage in relation to side-effects and quality of life. The reduced risk for coronary events with certain beta-blockers is probably independent of the reduction in blood pressure: possible mechanisms studied are cardiac anti-ischaemic effects, antifibrillatory effects, antiatherosclerotic and anti-thrombotic effects.
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PMID:Reducing the risk for coronary heart disease and stroke in hypertensives--comments on mechanisms for coronary protection and quality of life. 154 19

Bepridil is a calcium antagonist with a unique chemical structure and properties that differ from other calcium antagonists (e.g., a long half-life, sodium channel inhibition). In patients with normal left ventricular function, intravenous bepridil produces modest and short-lived reductions in heart rate and blood pressure. A transient negative inotropic effect is associated with higher doses (3-4 mg/kg). At the highest recommended oral dosage (400 mg/day), bepridil decreases resting heart rate and blood pressure; maximal exercise double product is not significantly reduced. In patients with impaired left ventricular function who are receiving oral bepridil 400 mg/day, virtually no distinguishable effects on heart rate, mean arterial pressure, pulmonary artery diastolic pressure or systemic vascular resistance were observed compared with placebo treatment. In patients with coronary disease, bepridil improves exercise hemodynamics (i.e., stroke volume index, cardiac index, ejection fraction) and reduces the frequency of wall motion abnormalities compared with placebo. Scintigraphic studies performed during stress suggest that compared with placebo, bepridil improves myocardial perfusion.
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PMID:Hemodynamic effects of bepridil in patients with coronary artery disease. 155 87

Measures to prevent ischemic stroke after aneurysmal subarachnoid hemorrhage include management of fluids to avoid dehydration, use of calcium entry blocking drugs, and when necessary, therapy with drug-induced hypertension and hypervolemic hemodilution. Promising treatments that may also prove to be effective include 21-aminosteroids, intrathecal thrombolytic therapy, and transluminal angioplasty.
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PMID:Prevention of brain ischemia after aneurysmal subarachnoid hemorrhage. 155 6

The three-vessel occlusion model of Kameyama et al. (Kameyama, M., Suzuki, J., Shirane, R. and Ogawa, A. (1985) Stroke 16, 489-493) was adapted with modifications to induce complete reversible rat forebrain ischemia. A fast and simple procedure for the isolation and purification of rat brain mitochondria, which provides high yield, is described. Mitochondria isolated from ischemic brain (12-30 min ischemia) exhibited decreases in State 3 respiratory rates of approx. 70% with NAD-linked respiratory substrates. Less effect was observed with succinate and rotenone. The State 4 respiratory activity remained near control levels except at 15 min of ischemia (25% increase) with NAD-linked substrates. Similarly, with succinate and rotenone, an approx. 30% increase in State 4 activity was observed at 20 min of ischemia. Consequently, the respiratory control indices (RCIs) were decreased. Both the respiratory rates and RCIs could be restored to near control levels upon the addition of EGTA(EDTA) or ruthenium red to the assay mixture. Analysis employing fura-2 as a Ca2+ probe, indicated a great decrease in the first order rate constant for Ca2+ uptake of ischemic mitochondria and a significant increase in Ca2+ homeostasis with an increase in the cytosolic Ca2+ concentration which results in excessive association of Ca2+ on the mitochondrial membrane and an inhibition of the respiratory chain-linked oxidative phosphorylation and Ca(2+)-transport activity of forebrain mitochondria. These deficits are proportional to the duration of ischemia.
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PMID:Ischemic injury to rat forebrain mitochondria and cellular calcium homeostasis. 155 46


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