pituitrin and Coronary-Disease

Congestive heart failure (CHF) represents a pathophysiologic state in which cardiac output is inadequate to meet the metabolic needs of multiple organ systems. The primary pathologic event in CHF is a marked, sustained reduction in the intrinsic contractility of the heart. A review of the current knowledge regarding the etiology and progression of CHF reveals that it is associated with profound biochemical, peripheral hemodynamic (increased peripheral vascular resistance), and electrolyte disturbances. In addition to sodium and water retention, CHF is often associated with hypokalemia and hypomagnesemia as well as tissue deficits in K and Mg. Cardiac glycosides and diuretics (loop and distal types) often exacerbate, or result in, hypokalemia and hypomagnesemia, which may lead to cardiac arrhythmias and sudden cardiac death. Deficits in extracellular and vascular tissue Mg lead to peripheral vasoconstriction; this together with K deficits and the release of neurohumoral substances may be responsible in large measure for the increase in peripheral vascular resistance commonly noted in CHF. More attention must be paid to the careful monitoring of electrolyte levels (Na, K, Mg) in tissues (possibly lymphocytes) and plasma of CHF patients. Deficits in either K or Mg must be corrected in CHF. The nonspecific vasodilator properties of Mg2+ together with its ability to unload the heart should be considered as an important adjunct tool in the management of CHF.

Topics: Adenosine Triphosphate; Calcium; Coronary Disease; Digitalis; Heart Failure; Humans; Magnesium; Magnesium Deficiency; Myocardial Contraction; Myocardium; Oxygen Consumption; Plants, Medicinal; Plants, Toxic; Potassium; Sodium; Vasopressins

Topics: Coronary Disease; Diuresis; Glomerular Filtration Rate; Hemodynamics; Humans; Kidney; Osmolar Concentration; Sodium; Vasopressins; Water; Water-Electrolyte Balance

Topics: Adenine Nucleotides; Angina Pectoris; Angiotensin II; Animals; Atrial Function; Blood Pressure; Coronary Disease; Coronary Vessels; Epinephrine; Histamine; Humans; Myocardium; Nitrates; Nitrites; Norepinephrine; Oxygen Consumption; Peptides; Piperazines; Prenylamine; Propranolol; Regional Blood Flow; Serotonin; Vasodilator Agents; Vasopressins; Verapamil

The purpose of this study was to determine whether endurance exercise training could buffer neuroendocrine activity in chronic heart failure patients.. Neuroendocrine activation is associated with poor long-term prognosis in heart failure. There is growing consensus that exercise may be beneficial by altering the clinical course of heart failure, but the mechanisms responsible for exercise-induced benefits are unclear.. Nineteen heart failure patients (ischemic disease; New York Heart Association [NYHA] class II or III) were randomly assigned to either a training group or to a control group. Exercise training consisted of supervised walking three times a week for 16 weeks at 40% to 70% of peak oxygen uptake. Medications were unchanged. Neurohormones were measured at study entry and after 16 weeks.. The training group (n = 10; age = 61 +/- 6 years; EF = 30 +/- 6%) and control group (n = 9; age = 62 +/- 7 years; EF = 29 +/- 7%) did not differ in clinical findings at study entry. Resting levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the training and control groups did not differ at study entry (5.6 +/- 1.3 pg/ml; 158 +/- 38 pg/ml; 6.1 +/- 2.0 pg/ml; 37 +/- 8 pg/ml training group vs. 4.8 +/- 1.2; 146 +/- 23; 4.9 +/- 1.1; 35 +/- 10 control group). Peak exercise levels of angiotensin II, aldosterone, vasopressin and atrial natriuretic peptide in the exercise and control groups did not differ at study entry. After 16 weeks, rest and peak exercise hormone levels were unchanged in control patients. Peak exercise neurohormone levels were unchanged in the training group, but resting levels were significantly (p < 0.001) reduced (angiotensin -26%; aldosterone -32%; vasopressin -30%; atrial natriuretic peptide -27%).. Our data indicate that 16 weeks of endurance exercise training modified resting neuroendocrine hyperactivity in heart failure patients. Reduction in circulating neurohormones may have a beneficial impact on long-term prognosis.

Topics: Aged; Aldosterone; Angiotensin II; Atrial Natriuretic Factor; Coronary Disease; Exercise; Female; Heart Failure; Humans; Male; Middle Aged; Neurosecretory Systems; Physical Endurance; Prognosis; Stroke Volume; Treatment Outcome; Vasopressins

We sought to examine whether long-term nitroglycerin treatment causes tolerance in large coronary arteries and whether the loss of vascular effects parallels neurohormonal adjustments.. Nitroglycerin therapy is associated with increased plasma renin activity and aldosterone levels and a decrease in hematocrit. It is assumed that nitroglycerin tolerance results in part from these neurohormonal adjustments and intravascular volume expansion.. Three groups were studied: group I (n = 10), no prior nitroglycerin therapy; and group II (n = 10) and group III (n = 8), 24- and 72-h long-term nitroglycerin infusion (0.5 micrograms/kg body weight per min), respectively. Coronary artery dimensions were assessed using quantitative angiography. Plasma renin activity, plasma aldosterone and vasopressin levels and hematocrit were monitored before and during nitroglycerin infusions.. In group I, increasing intravenous concentrations of nitroglycerin caused a dose-dependent increase of the midportion of the left anterior descending coronary artery (baseline diameter 2.13 +/- 0.07 mm [mean +/- SEM], maximally by 22 +/- 2%) and left circumflex coronary artery (baseline diameter 2.08 +/- 0.07) mm, maximally by 22 +/- 3%). An intracoronary nitroglycerin bolus (0.2 mg) caused no further significant increase in diameter, indicating maximal dilation. In group II (n = 10), the baseline large coronary artery diameter under ongoing nitroglycerin was significantly larger than that in group I (left anterior descending artery 2.61 +/- 0.08 mm, left circumflex artery 2.57 +/- 0.08 mm). Additional intravenous and intracoronary nitroglycerin challenges did not cause further dilation, indicating maximally dilated vessels. At the same time, plasma renin activity, plasma aldosterone and vasopressin levels were significantly increased, and hematocrit significantly decreased. In group III patients, the baseline diameter of the left anterior descending artery and the left circumflex artery did not differ from that in patients without nitroglycerin pretreatment, indicating a complete loss of nitroglycerin coronary vasodilative effects. These patients showed no significant increase in circulating neurohormonal levels but a significant decrease in hematocrit.. Within 24 h of continuous nitroglycerin treatment, the coronary arteries were maximally dilated despite neurohormonal adjustments and signs of intravascular volume expansion. Within 3 days of nitroglycerin infusion, tolerance developed in the absence of neurohormonal activation. The dissociation of neurohormonal adjustments and tolerance in large coronary arteries indicates that after long-term nitroglycerin treatment, true vascular tolerance, perhaps from an intracellular tolerance step, may have developed.

Topics: Aldosterone; Case-Control Studies; Coronary Angiography; Coronary Disease; Coronary Vessels; Dose-Response Relationship, Drug; Drug Tolerance; Female; Hematocrit; Humans; Male; Middle Aged; Nitroglycerin; Renin; Time Factors; Vasodilation; Vasodilator Agents; Vasopressins

In 20 patients with established coronary artery disease, stable angina pectoris and reproducible ST-segment depression, the pharmacokinetics and pharmacodynamic effects of 60 mg slow-release isosorbide-5-mononitrate (IS-5-MN) (10 patients) after a 7-day therapy were compared with those of a placebo group (10 patients) using a randomized double-blind, placebo-controlled study design. Ten patients could be controlled after long-term therapy over a mean of 399 +/- 111 days. There was no significant change under IS-5-MN of either blood pressure, heart rate, rate-pressure product, or myocardial oxygen consumption. Treatment over one week significantly reduced ST-segment depression 4 and 8 h after drug intake (38-48% of the placebo value, p less than 0.01). Maximum reduction in ST-segment depression was found 4 and 8 h after IS-5-MN intake both after one-week and long-term therapy at the time of peak plasma drug concentration (341 +/- 95 and 405 +/- 125 ng/ml, respectively). At a residual plasma concentration below 100 ng/ml, ST depression was not significantly improved 24 h after drug intake compared with placebo. Technetium-99m ventriculography showed an insignificant increase in ejection fraction and a slight reduction of ventricular volumes after both short- and long-term therapy with IS-5-MN (p greater than 0.05). The drug's plasma levels were higher under chronic than under short-term therapy which may be due to enzyme saturation. Maximum IS-5-MN plasma concentrations at a mean of 445 +/- 116 ng/ml were reached after 5.8 +/- 2.9 h. Beta-phase half-life of elimination was 9 +/- 3 h. IS-5-MN administered as a single 60 mg dose of a slow-release preparation/day proved to have a favorable pharmacokinetic profile as well as an efficient antiischemic activity after both short- and long-term therapy. Problems of tolerance or activation of hormonal counter-regulation due to vasodilation were not observed.

Topics: Adult; Aged; Angiotensin II; Blood Pressure; Coronary Disease; Delayed-Action Preparations; Double-Blind Method; Electrocardiography; Epinephrine; Heart Rate; Humans; Isosorbide Dinitrate; Middle Aged; Neurotransmitter Agents; Norepinephrine; Oxygen Consumption; Placebos; Renin; Time Factors; Vasopressins; Ventricular Function, Left

To examine the coronary effects of arginine-vasopressin during reperfusion after a short ischemia, left circumflex coronary artery flow was electromagnetically measured, and 15 min total occlusion of this artery followed by reperfusion was induced in anesthetized goats (five nontreated, five treated with the inhibitor of nitric oxide synthesis Nomega-nitro-L-arginine methyl ester (L-NAME) and five treated with the inhibitor of cyclooxygenase meclofenamate). The vasoactive drugs and L-NAME were intracoronarily injected, and meclofenamate by i.v. route. At 60 min of reperfusion, coronary vascular conductance was not changed significantly in nontreated and was decreased by 35% (P<0.01) in L-NAME-treated and by 30% (P<0.01) in meclofenamate-treated animals. During reperfusion, the coronary vasodilatation with acetylcholine (3-100 ng) and sodium nitroprusside (1-10 microg) was not altered in nontreated animals, and the vasodilatation with acetylcholine but not with sodium nitroprusside was partially decreased in L-NAME--but not in meclofenamate-treated animals. The vasoconstriction in response to arginine-vasopressin (0.03-0.3 microg) was increased during reperfusion in nontreated, was not changed in L-NAME-treated and was decreased in meclofenamate-treated animals. Therefore, it is suggested that during reperfusion after a short ischemia: (1) the coronary vasodilator reserve is preserved; (2) the coronary vasodilatation with acetylcholine is also preserved, but in this vasodilatation, the role of nitric oxide may be attenuated and prostanoids may be not involved; and (3) the coronary vasoconstriction with arginine-vasopressin is increased, probably due to both attenuation of the modulatory role of nitric oxide and the release of vasoconstrictor prostanoids.

Topics: Acetylcholine; Anesthesia; Animals; Blood Pressure; Coronary Circulation; Coronary Disease; Enzyme Inhibitors; Female; Goats; Heart Rate; Hemodynamics; Ischemia; NG-Nitroarginine Methyl Ester; Nitric Oxide; Nitric Oxide Synthase; Nitroprusside; Prostaglandins; Reperfusion; Vasoconstrictor Agents; Vasodilator Agents; Vasopressins

The effects of SMP-300, an orally active, potent, and selective Na+/H+ exchange inhibitor, were evaluated and compared with those of nifedipine, propranolol, and nicorandil on three experimental angina models and on myocardial infarction in rats. SMP-300 (0.1-1 mg/kg, p.o.) reduced isoproterenol-induced ST segment depression in a dose-dependent manner. Its maximal effect was comparable to that reported for propranolol and greater than that of nifedipine. SMP-300 (0.3-1 mg/kg) reduced vasopressin-induced ST segment depression in a dose-dependent manner, and its maximal effect was comparable to those of nifedipine and nicorandil. SMP-300 (0.3-1 mg/kg, p.o.) and propranolol (100 mg/kg, p.o.) inhibited coronary artery occlusion-induced T-wave elevation, but nifedipine (3 mg/kg, p.o.) did not. SMP-300 (1 mg/kg, p.o.) reduced myocardial infarct size after 40 min of coronary artery occlusion followed by 24 h of reperfusion, but nifedipine (3 mg/kg, p.o.) or propranolol (100 mg/kg, p.o.) did not. This study provides support for the future use of a Na+/H+ exchange inhibitor as an anti-anginal drug with a novel mode of action.

Topics: Administration, Oral; Angina Pectoris; Animals; Azocines; Coronary Disease; Electrocardiography; Isoproterenol; Male; Myocardial Infarction; Myocardial Reperfusion Injury; Myocardium; Nicorandil; Nifedipine; Propranolol; Pyrroles; Rats; Rats, Sprague-Dawley; Rats, Wistar; Sodium-Hydrogen Exchangers; Vasodilator Agents; Vasopressins

Initial morphological and cytochemical cardiomyocyte alterations were studied at experimental acute coronary failure by histological, electron microscopy and electron histochemical methods. The results obtained demonstrated that transition of contractile myocardium to emergency function occurring at experimental conditions is accompanied by a strict rise of structural and functional heterogeneity. Prior to this process a functional and conformational unification of mitochondria takes place, passing to progress of pathological process, destructive changes of organellae causing cell death. Appearance of cellular insufficiency is acting upon all energy dependent processes: contractile cycle efficiency, function of calcium transferring systems Ca-binding sarcoplasmic reticulum function and that of mitochondria, as well efficiency of regenerative mechanisms. In appearing condition ruining of every cardiomyocyte system is possible.

Topics: Acute Disease; Animals; Coronary Disease; Disease Models, Animal; Histocytochemistry; Microscopy, Electron; Myocardium; Rabbits; Time Factors; Vasoconstrictor Agents; Vasopressins

Although it has been postulated that minimally invasive cardiac surgery using the port access method would reduce operative stress and postoperative pain and accelerate postoperative recovery to a good quality of life, few data are currently available to document this intuitively appealing claim. Therefore, this study was designed to examine differences in stress response, postoperative pain, rapidity of recovery, and quality of life after port access (PA) isolated coronary artery bypass surgery compared with standard sternotomy (STD) isolated coronary bypass surgery.. Fourteen PA and 15 STD coronary bypass patients were studied postoperatively for pain score, FEV, catecholamine and cortisol levels, resumption of activity, and Duke Activity Scale ratings. The surgical approach was based on the surgeon's preference. Although the PA patients were younger, there were no other differences between the groups in gender or preoperative risk factors.. There were no operative deaths and no differences between the groups in perioperative complications. Repeated measures analysis of variance showed lower pain scale ratings over the first 4 postoperative weeks in the PA group (P < 0.001). The PA patients also had less muscle soreness, shortness of breath, fatigue, and poor appetite at 1, 2, 4, and 8 weeks (P < 0.05), better FEV at 1 day (1.59 vs. 0.97 l/s; P < 0.02) and 3 days (2.20 vs. 1.49 l/s; P < 0.03), and lower norepinephrine levels at days 1, 2, and 3 (P = 0.005). The Duke Activity Scale questionnaire results demonstrated that more PA patients were able to walk 1-2 blocks at 1 week, climb stairs at 1 and 2 weeks, perform light or moderate housework at 1 and 2 weeks, and engage in moderate recreational activities and perform heavy housework at 4 and 8 weeks (P < 0.05).. These results show that compared with STD coronary bypass patients PA patients enjoyed significant postoperative physiologic and quality of life advantages with less pain, less early stress response, better pulmonary function, and superior Duke Activity scores during the first 2 postoperative months.

Topics: Aged; Biomarkers; Catecholamines; Coronary Artery Bypass; Coronary Disease; Female; Humans; Hydrocortisone; Male; Middle Aged; Minimally Invasive Surgical Procedures; Pain Measurement; Pain, Postoperative; Quality of Life; Retrospective Studies; Sternum; Stress, Physiological; Surveys and Questionnaires; Thoracotomy; Treatment Outcome; Vasopressins

Mature coronary collateral arteries are hyperresponsive to vasopressin; in contrast, contractile responses of collaterals to endothelin are attenuated. Our goal was to determine the cellular mechanisms underlying these differences in reactivity using two sizes of canine collateral arteries isolated from hearts subjected to chronic coronary occlusion.. Contractile responses to vasopressin (100 mmol/L) were enhanced threefold to fourfold in near-resistance (approximately 200 microns lumen diameter) and conduit (approximately 500 microns lumen diameter) collateral arteries compared with similarly sized noncollateral coronary arteries (P < .01). In contrast, contractions of both sizes of collaterals in response to endothelin (0.01 to 30 nmol/L) were smaller than responses of size-matched noncollateral arteries (P < .05). Pretreatment with either indomethacin (5 mumol/L), a cyclooxygenase inhibitor, or NG-nitro-L-arginine methyl ester (100 mumol/L), a nitric oxide synthase inhibitor, did not alter the relative responsiveness of collateral arteries to vasopressin or endothelin compared with noncollateral arteries. Vasopressin produced greater increases of intracellular free Ca2+ (measured by use of fura-2 microfluorometry and Ca(2+)-dependent 42K+ efflux) in smooth muscle of collateral arteries than in smooth muscle of noncollateral arteries (P < .05). Surprisingly, endothelin-induced increases of Ca2+ were not different in smooth muscle of collateral and noncollateral arteries (P > .05).. We conclude that altered contractile responsiveness of collateral arteries to vasopressin and endothelin does not result from altered synthesis/release of nitric oxide or prostaglandins. Parallel enhancement of vasopressin-mediated Ca2+ and contractile responses suggests increases in vasopressin receptor number, affinity, and/or efficiency of coupling mechanisms in collateral smooth muscle. The dissociation between endothelin-induced contractile and Ca2+ responses of collaterals indicates that the mechanisms involved in increasing Ca2+ sensitivity of contractile proteins during endothelin stimulation may be altered in collateral arteries.

Topics: Animals; Calcium; Collateral Circulation; Coronary Disease; Coronary Vessels; Culture Techniques; Cyclooxygenase Inhibitors; Dogs; Endothelins; Male; Muscle, Smooth, Vascular; Nitric Oxide Synthase; Potassium; Vasoconstriction; Vasopressins

Ischemia and reperfusion alter the reactivity of large coronary arteries, but the effect of ischemia and reperfusion on the coronary microcirculation has been less well defined. Elevated circulating levels of vasopressin are associated with cardiopulmonary bypass and numerous other clinical states in which vascular ischemia and reperfusion may occur. We examined the effects of ischemia with and without reperfusion on the responses to vasopressin of both large coronary arteries and coronary arterial microvessels. Studies were performed on vessels from control dogs (n = 8), dogs undergoing 1 hour of ischemia only (n = 8), and dogs undergoing 1 hour of ischemia followed with 1 hour of reperfusion (n = 9). Rings of proximal obtuse marginal coronary arteries distal to the site of circumflex coronary artery occlusion were studied in isolated organ chambers. Coronary microvessels (110 to 220 microns in diameter) were studied in a pressurized (20 mm Hg), no-flow state with a microvessel imaging apparatus and electronic dimension analyzer. Microvessels were preconstricted with the thromboxane A2 analog U46619. Responses of large vessel rings were studied in the nonpreconstricted state and after preconstriction with prostaglandin F2 alpha. Large vessel response to vasopressin was minimal and not altered by ischemia with or without reperfusion. In contrast, ischemia markedly affected the coronary microvascular response to vasopressin (10 to 1000 microU/ml). Control coronary microvessels constricted minimally to vasopressin (4% +/- 2% of the baseline diameter), while microvessels after either ischemia alone or ischemia followed by reperfusion constricted 22% +/- 5% and 21% +/- 3%, respectively (p less than 0.05 versus control for both). Hemoglobin, which inactivates the endothelium-derived relaxing factor, augmented microvascular constrictions to vasopressin in all groups to a similar extent. Relaxations to the endothelium-independent agent nitroglycerin were not altered by ischemia. Constrictions of the coronary microcirculation to vasopressin in conditions such as cardiopulmonary bypass or myocardial ischemia, in which circulating levels of vasopressin are increased, may predispose to persistent myocardial ischemia in the perioperative setting.

Topics: Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Dinoprost; Dogs; Microcirculation; Myocardial Reperfusion; Myocardial Reperfusion Injury; Nitroglycerin; Prostaglandin Endoperoxides, Synthetic; Vasoconstriction; Vasopressins

A study of neurohumoral and functional determinants of the advance of Ischemic heart disease in 39 patients with unstable stenocardia with positive results of loading tests (transesophageal electrocardiostimulation and veloergometry) allowed to reveal a significant reduction of the coronary reserve and regional dysfunction of the myocardium that interrelated with changes of the prostacyclin/thromboxane balance, increase of vasopressin with unchanged angiotensin II value and increased marker of the functional state of thrombocytes--beta-thromboglobulin. These changes may be one of the leading links in the pathogenesis of destabilization.

Topics: Acute Disease; Angiotensin II; beta-Thromboglobulin; Coronary Disease; Epoprostenol; Fibrinopeptide A; Humans; Physical Exertion; Radioimmunoassay; Thromboxane A2; Vasopressins

This study was performed to test the hypothesis that active constriction of coronary collateral vessels can worsen hypoperfusion of collateral-dependent myocardium during exercise. Studies were performed in seven adult mongrel dogs in which intermittent followed by permanent occlusion of the left circumflex coronary artery produced an area of collateral-dependent myocardium without gross evidence of infarct. Myocardial blood flow was determined with microspheres while measurement of aortic and distal coronary pressures allowed calculation of collateral and small vessel resistance at rest and during treadmill exercise. The ability of collateral vessel constriction to limit blood flow was assessed by infusion of vasopressin during exercise. During control conditions, blood flow in the collateral zone underwent a subnormal increase during exercise in comparison with the normal zone (1.74 +/- 0.27 versus 2.50 +/- 0.40 ml/min/g, respectively, p less than 0.05). Infusion of vasopressin in a dose that caused no change in normal zone flow (0.01 microgram/kg/min i.v.) produced a 30 +/- 5% further decrease in flow to the collateral zone (p less than 0.01). This decrease in collateral zone flow resulted from a 48 +/- 14% increase in transcollateral resistance in response to vasopressin infusion (p less than 0.01), as well as a 40 +/- 9% increase in small vessel resistance in the collateral zone (p less than 0.01). These data demonstrate that active constriction of both collateral vessels and coronary resistance vessels can contribute to hypoperfusion of collateral-dependent myocardium during exercise.

Topics: Animals; Collateral Circulation; Coronary Circulation; Coronary Disease; Coronary Vessels; Dogs; Female; In Vitro Techniques; Male; Microspheres; Physical Exertion; Vascular Resistance; Vasoconstriction; Vasopressins

Previous in vivo studies have shown that vasopressin, which releases the endothelium-derived relaxing factor and constricts coronary smooth muscle, produces augmented constriction of coronary microvessels perfused by mature collaterals. We hypothesized that chronic perfusion through collaterals produces endothelial dysfunction in the recipient vasculature. Mature collaterals were stimulated in mongrel dogs by the ameroid constrictor technique. After 3-6 months, rings of conduit vessels (obtuse marginals) were studied in organ chambers, and coronary microvessels (100-220 microns) were studied in a pressurized, no-flow state with a microvessel imaging apparatus. Eleven dogs were used as controls. Large vessels were preconstricted with prostaglandin F2 alpha to 30-70% of the maximum potassium chloride tension, and microvessels were preconstricted to 20-60% of the baseline diameter with the thromboxane mimetic U46619. Relaxations to the receptor-mediated agents acetylcholine and ADP were markedly impaired in collateral-dependent coronary microvessels, whereas relaxations to nitroglycerin were enhanced compared with microvessels from control dogs. Relaxation to the calcium ionophore A23187, which releases the endothelium-derived relaxing factor through nonreceptor-mediated mechanisms, were similar in control and ameroid microvessels. Constriction to vasopressin was augmented in collateral-dependent microvessels compared with controls. Responses to all agonists were similar between control and collateral-dependent large vascular rings. In conclusion, chronic perfusion through collateral vessels selectively impairs receptor-mediated endothelium-dependent relaxations and augments constriction to vasopressin in the coronary microcirculation. These findings may have important implications regarding neurohumoral regulation of perfusion to collateral-dependent myocardium.

Topics: Acetylcholine; Adenosine Diphosphate; Animals; Calcimycin; Collateral Circulation; Coronary Circulation; Coronary Disease; Dogs; Endothelium, Vascular; Female; In Vitro Techniques; Male; Nitroglycerin; Potassium Chloride; Vasoconstriction; Vasopressins

Vasopressin, the renin-angiotensin system and atrial natriuretic factor (ANF) interact in regulating blood pressure. While the vasoconstrictor effect of vasopressin and the renin-angiotensin system is well documented, the direct vascular effect of ANF is unclear. We studied in anaesthetized dogs the coronary vascular effects of agonists and antagonists of vasopressin and the renin-angiotensin system under control and ischaemic conditions, respectively. In addition, the action of ANF and its relationship to the renin-angiotensin system was analysed. A coronary artery was cannulated and perfused by a bypass system from the femoral arteries of the same animal. Coronary vasoconstriction by vasopressin was potentiated when myocardial ischaemia was induced by lowering coronary perfusion pressure while coronary constriction by angiotension I and II was mitigated. A vasopressin receptor blocker slightly reduced coronary blood flow at high doses (intrinsic activity) while the angiotensin II receptor blocker increased coronary flow in myocardial ischaemia. ANF effects were ambiguous at lower doses (1 ng (kg)-1 i.c.) with coronary constriction in 79% of dogs. At higher doses (1 microgram kg-1) ANF consistently induced coronary dilation. The angiotensin II receptor blocker saralasin significantly reduced this coronary dilator effect of ANF. Thus, in conclusion, a vasoconstrictor effect of endogenous vasopressin could not be shown by this study. In contrast, endogenous angiotensin II might participate in control of coronary blood flow during myocardial ischaemia. The coronary dilator effect of ANF at least in part appears to be due to interference with the renin-angiotensin system.

Topics: Angiotensin II; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Captopril; Coronary Circulation; Coronary Disease; Dogs; Renin-Angiotensin System; Saralasin; Vasoconstriction; Vasopressins

In the present study, 52 patients with cirrhosis, portal hypertension, and variceal hemorrhage underwent either an elective or an emergency side-to-side portacaval shunt operation. Vasopressin was infused intravenously at 60 units/hour from just prior to abdominal incision until completion of the anastomosis. Eight of 35 patients who received vasopressin alone (23 percent) tolerated increased doses of 75 to 90 units/hour to obtain hemostasis. Four of 52 patients required simultaneous infusion of sodium nitroprusside to correct systemic hypertension. An additional 15 percent reduction in portal venous pressure occurred in these patients. Eleven of 13 patients with vasopressin-induced myocardial ischemia responded to simultaneous infusion of nitroglycerin. Further prospective studies are indicated to adequately delineate the dose and duration of therapy with either nitroprusside or nitroglycerin for simultaneous administration with intravenous vasopressin.

Topics: Adult; Aged; Coronary Disease; Drug Therapy, Combination; Esophageal and Gastric Varices; Female; Ferricyanides; Gastrointestinal Hemorrhage; Humans; Intraoperative Period; Male; Middle Aged; Nitroglycerin; Nitroprusside; Portacaval Shunt, Surgical; Retrospective Studies; Vasopressins

Topics: Aged; Aldosterone; Atrial Natriuretic Factor; Cardiac Pacing, Artificial; Coronary Disease; Electrophysiology; Female; Hemodynamics; Humans; Hydrocortisone; Male; Middle Aged; Norepinephrine; Renin; Tachycardia; Vasopressins

Blood vasopressin, tri-iodothyronine, total thyroxine, thyrotrophic hormone, cortisol, ACTH and insulin levels were measured in 60 chronic coronary patients aged 35 to 70. Coronary patients showed elevated blood vasopressin, particularly in the presence of frequently recurring anginal attacks. There was no significant difference in vasopressin levels of patients with and without attendant essential hypertension, those with atherosclerotic and postinfarction cardiosclerosis, or in relation to body weight. Insulin, cortisol, adrenocorticotrophic and thyrotrophic hormones were significantly increased, and tri-iodothyronine and total thyroxine, significantly decreased, in coronary patients as compared to the controls.

Topics: Adrenocorticotropic Hormone; Adult; Aged; Chronic Disease; Coronary Disease; Humans; Hydrocortisone; Insulin; Male; Middle Aged; Thyroid Hormones; Vasopressins

Topics: Adult; Aged; Anesthesia, Intravenous; Cardiac Surgical Procedures; Catecholamines; Coronary Disease; Humans; Intraoperative Period; Middle Aged; Mitral Valve Stenosis; Vasopressins

Tobacco smoking increases the risk of myocardial infarction and sudden death. When used for diagnostic and therapeutic ends, vasopressin, at low doses, may induce acute ischaemic complications in patients with coronary artery disease. This study showed that in some patients the inhalation of tobacco smoke caused a rise in plasma vasopressin and nicotine-stimulated-neurophysin, a substance easily measured and used as a marker of vasopressin secretion because of the close relationship of the two substances. Twelve out of twenty five subjects presented higher levels of nicotine-stimulated-neurophysin than the normal for the same group before smoking (p less than 0,005): 280 +/- 54 compared to 714 +/- 459 pg/ml. Simultaneous measurement of vasopressin and nicotine-stimulated-neurophysin every 5 minutes in 4 subjects confirmed the parallel changes of these substances during smoking. These results suggest that vasopressin may play a primary role in the acute ischaemic complications of tobacco smoking. The concept of the "vasopressin response" could be used as a biological parameter to identify subjects at "high cardiovascular risk" under the effects of tobacco and so lead to a prophylactic strategy aimed more specifically at these patients.

Topics: Coronary Disease; Humans; Neurophysins; Risk; Smoking; Vasopressins

[(5Z,13E,9 alpha,11 alpha,15S)-2,3,4-Trinor - 1,5 - inter-m - phenylene - 6,9 - epoxy - 11,5 - dihydroxy - 15 - cyclohexyl - 16,17,18,19,20-pentanor]- prosta-5,13-dienoic acid (sodium salt) (CG 4203) is a new stable epoprostenol (prostacyclin) analogue with a relative platelet antiaggregatory potency of 0.46 (ADP aggregation in vitro) and a hypotensive potency of 0.14 (anaesthetized rat i.v.) as compared to epoprostenol. In isolated perfused rat hearts, CG 4203 (4.64 X 10(-9) mol/l) significantly attenuated arrhythmias and loss of left ventricular creatine kinase (CK) activity observed in control hearts after 30 min perfusion with hypoxic and 30 min reperfusion with oxygenated Krebs-Ringer solution. In anaesthetized rats, CG 4203 (1.0 microgram X kg-1 X min-1 i.v.) significantly reduced incidence of ventricular fibrillation and increase in plasma CK activity after ligation of the left coronary artery. Infusion of 1.0 and 2.15 micrograms X kg-1 X min-1 CG 4203 i.v. in anaesthetized rats dose-dependently inhibited electrocardiographic changes, i.e. ST depression observed after i.v. injection of 1.0 IU X kg-1 vasopressin. In rat models of sustained myocardial hypoxia, myocardial infarction, and transient cardiac ischemia, CG 4203 thus exerts cardioprotective effects which, depending on the model considered, may be ascribed to either its vasodilatory, coronary dilatory, antiaggregatory or epoprostenol-like cytoprotective activity.

Topics: Animals; Cardiovascular Agents; Coronary Disease; Creatine Kinase; Epoprostenol; In Vitro Techniques; Male; Myocardial Contraction; Nitroglycerin; Oxygen; Perfusion; Rats; Rats, Inbred Strains; Vasopressins

It has been demonstrated in experiments on rats that acute myocardial ischemia gives rise to a decrease in diuresis, elevation of antidiuretic activity of blood plasma and the blood concentration of immunoreactive aldosterone. Intraperitoneal injection of a synthetic enkephalin analog D-ala2-leu5-arg6-enkephalin in a dose of 1.25 nmol/kg bw resulted in partial normalization of diuresis, reduction in antidiuretic activity of blood plasma and blood aldosterone level to the control values. Naloxone eliminated the effects described. It is concluded that enkephalins have an inhibitory action on aldosterone and vasopressin secretion, with this action being mediated via opiate receptors.

Topics: Aldosterone; Animals; Coronary Disease; Diuresis; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Male; Naloxone; Rats; Vasopressins

Blood platelets participating in the formation of haemostatic plugs or thrombi are likely to be exposed to combinations of several agonists. We have found that platelet aggregation and the release reaction are enhanced by combinations of the hormones adrenaline, noradrenaline, vasopressin and 5 hydroxytryptamine acting synergistically at levels obtained in circulating blood for three of these hormones. If surges of adrenaline and other hormones sensitize platelets this may provide a link between some of the risk factors and coronary heart disease.

Topics: Adult; Blood Platelets; Coronary Disease; Epinephrine; Hormones; Humans; Norepinephrine; Platelet Aggregation; Serotonin; Stress, Physiological; Thromboembolism; Vasopressins

Topics: Aged; Arrhythmias, Cardiac; Coronary Disease; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Humans; Male; Vasopressins

A 59-year-old man with severe variceal bleeding received therapy with intravenously administered vasopressin and cimetidine. Inappropriate bradycardia, sinoatrial and atrioventricular blocks, and terminal bradycardia leading to asystole, occurred during bleeding, with the greatest number of rhythm abnormalities occurring during combined cimetidine and vasopressin therapy. The results of post-mortem examination showed only mild coronary artery disease. The hazards of combined vasopressin and cimetidine therapy are reviewed.

Topics: Arrhythmias, Cardiac; Bradycardia; Cimetidine; Coronary Disease; Drug Therapy, Combination; Electrocardiography; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Guanidines; Heart Block; Humans; Male; Middle Aged; Vasopressins

The hormonal responses to anaesthesia and cardiac surgery were studied in patients undergoing valve or coronary bypass surgery. Marked increases in antidiuretic hormone levels as a result of surgical stress were seen, and were of approximately equal magnitude in both groups. Although both groups also showed marked increases in plasma cortisol levels in response to operations, this response appeared to be relatively blunted in valve surgery patients, especially at the end of operation and in the intensive care unit. This blunted cortisol response may be a manifestation of exhaustion of adrenocortical reserves in valvular surgical patients whose sympathoadrenal system has already been chronically stimulated by a low output state. The important role of the neuroendocrine system in maintaining homeostasis postoperatively has long been recognized; this relative cortisol deficiency may be aetiologically related to poor postoperative recovery in critically ill valvular surgery patients.

Topics: Coronary Disease; Heart Valve Diseases; Hemodynamics; Humans; Hydrocortisone; Middle Aged; Stress, Physiological; Vasopressins

Topics: Adult; Aged; Aortic Valve; Cardiopulmonary Bypass; Coronary Artery Bypass; Coronary Disease; Electrolytes; Heart Valve Diseases; Hemodynamics; Humans; Male; Middle Aged; Mitral Valve; Osmolar Concentration; Urine; Vasopressins

Topics: Animals; Coronary Disease; Myocardial Contraction; Myocardium; Rabbits; Vasopressins

The blood vasopressin content and kinin system activity were studied in 83 patients with chronic ischemic heart disease of various severity. It was established that the blood vasopressin concentration increases with an increase in the severity of the disease. A high degree of correlation between changes in vasopressin content and in components of the kinin system was revealed: increase in the concentration of vasopressin is attended by activation of the kallikrein-kinin system. The mechanisms of the interrelationship of the vasopressin and kinin content are discussed. It is suggested that vasopressin may play a role in the pathogenesis of chronic ischemic heart disease.

Topics: Adult; Chronic Disease; Coronary Angiography; Coronary Disease; Esterases; Humans; Kallikreins; Kinins; Lysine Carboxypeptidase; Middle Aged; Vasopressins

Short-time disturbances of the microcirculation in rabbits had a different influence on the ATP-ase activity of smooth and rough microsomes of the liver and heart. Mg+2ATP-ase activity in the liver decreased in both microsome fractions; as in the heart, the enzyme activity increased only in the smooth (light) microsomes.

Topics: Acute Disease; Adenosine Triphosphatases; Animals; Coronary Disease; Dextrans; Enzyme Activation; Glucose-6-Phosphatase; Male; Microcirculation; Microsomes; Microsomes, Liver; Myocardium; Rabbits; Time Factors; Vasopressins

Topics: Adenosine Triphosphate; Angiotensins; Animals; Arachidonic Acids; Bradykinin; Coronary Disease; Indomethacin; Kidney; Lipase; Myocardium; Prostaglandins; Rabbits; Tachyphylaxis; Vasopressins

The effect of 0.15 IU/min vasopressin (VA) administered intracoronarily on postocclusion reactions following 15 sec, 30 sec, 60 sec, and 120 sec occlusions of the left coronaries of the isolated fibrillating dog heart were studied at constant pressure or constant volume perfusion with arterial blood of another dog. Basal perfusion pressure was kept at the level of 150 mmHg. Preocclusion state and postocclusion reactions were characterized by changes in coronary conductance. Peak conductance, maximum conductance, reactivity, time to peak conductance, mean transit time and repayment were computed for characterizing reactive hyperaemia. In the control state the post-occlusive conductance--time curve was higher, but shorter in duration with constant pressure perfusion than with constant volume perfusion. Upon the administration of VA, basal conductance decreased considerably while with constant pressure perfusion the hyperaemic reactions underwent hardly any change. In contrast, using constant volume perfusion, the duration of reactive hyperaemia was shortened by VA. Consequently, the differences in mean transit time observed in the controls resulted from the unequal perfusion techniques disappeared on the application of VA. On both constant pressure and constant volume perfusion, maximum conductance decreased as a result of the decrease in basal conductance, therefore the reactivity of the coronary vessels increased markedly. It is concluded that myogenic vasorelaxation may contribute to reactive hyperaemic responses not only on brief, but also on prolonged occlusion. The basal vascular tone is of importance in the coronary adaptation to ischaemia.

Topics: Animals; Blood Circulation; Coronary Disease; Dogs; Heart; Hyperemia; Myocardium; Perfusion; Vasopressins

Topics: Catecholamines; Coronary Disease; Glucocorticoids; Hormones; Humans; Insulin; Prostaglandins; Thyroid Hormones; Vasopressins

Experimental results showed that the ECG changes (elevation of T wave, a shift of the S-T segment and disturbances of the atrio-ventricular conduction) under the effect of vasopressin occurred in rats aged 24-26 months after lower doses of vasopressin than in the animals aged 10-12 months. With the administration of the same doses coronary insufficiency was more pronounced in the old animals (more frequent disturbances of the atrio-ventricular conduction, grade II or III, and greater derangement of general hemodynamics).

Topics: Age Factors; Animals; Coronary Disease; Electrocardiography; Heart Conduction System; Male; Rats; Vasopressins

Topics: Adult; Aged; Aging; Animals; Arrhythmias, Cardiac; Cardiovascular Diseases; Cerebrovascular Disorders; Coronary Disease; Humans; Hypertension; Middle Aged; Rabbits; Rats; Vasopressins

Topics: Coronary Disease; Diuresis; Glomerular Filtration Rate; Humans; Kidney; Osmolar Concentration; Sodium; Vasopressins; Water; Water-Electrolyte Balance

Topics: Animals; Coronary Disease; Dogs; Ischemia; Vasopressins; Vectorcardiography

Topics: Animals; Coronary Disease; Coronary Vessels; Dogs; Kallikreins; Lactates; Male; Metabolic Diseases; Myocardium; Vasopressins

Topics: Adult; Arrhythmias, Cardiac; Cardiac Output; Coronary Circulation; Coronary Disease; Electrocardiography; Esophageal and Gastric Varices; Female; Gastrointestinal Hemorrhage; Humans; Muscle, Smooth; Vasopressins

Topics: Amino Acids; Animals; Cetacea; Chromatography, Ion Exchange; Chromatography, Paper; Coronary Disease; Electrocardiography; Hypoxanthines; Myocardium; Nucleosides; Nucleotides; Rats; Tissue Extracts; Vasopressins

Topics: Adolescent; Adult; Aged; Aldosterone; Coronary Disease; Female; Heart Failure; Humans; Male; Middle Aged; Pulmonary Heart Disease; Rheumatic Heart Disease; Vasopressins; Water-Electrolyte Balance

Topics: Aminophylline; Animals; Arrhythmias, Cardiac; Coronary Disease; Electrocardiography; Propranolol; Rats; Vasopressins

Topics: Animals; Arteriosclerosis; Cholesterol; Coronary Disease; Dietary Fats; Rabbits; Reserpine; Vasopressins

Topics: Animals; Arteriosclerosis; Cholesterol; Coronary Disease; Coronary Vessels; Epinephrine; Ethanol; Exercise Test; Hypoxia; Isoproterenol; Male; Norepinephrine; Rabbits; Vasopressins

Topics: Acetylcholine; Amino Alcohols; Aminobenzoates; Angiotensin II; Animals; Benzoates; Coronary Disease; Coronary Vessels; Dilatation; Dipyridamole; Dogs; Guanethidine; Isoproterenol; Models, Biological; Nitroglycerin; Norepinephrine; Prenylamine; Propranolol; Strophanthins; Vasodilator Agents; Vasopressins

Topics: Animals; Colloids; Coronary Disease; Coronary Vessels; Dextrans; Electrocardiography; Erythrocyte Aggregation; Myocardial Infarction; Rabbits; Vasopressins

Topics: Animals; Anuria; Coronary Disease; Denervation; Diuresis; Dogs; Hypophysectomy; Kidney; Methods; Parabiosis; Pituitary Gland, Posterior; Vasopressins

Topics: Animals; Coronary Disease; Electrocardiography; Guinea Pigs; Pituitary Hormones, Posterior; Rabbits; Rats; Vasopressins

Topics: Angina Pectoris; Coronary Disease; Digoxin; Electrocardiography; Hydrochlorothiazide; Hypercholesterolemia; Hypertension; Metaraminol; Nitroglycerin; Shock; Shock, Cardiogenic; Vasopressins; Warfarin

Topics: Acetylcholine; Animals; Arteriosclerosis; Atherosclerosis; Blood Chemical Analysis; Blood Proteins; Cholesterol; Choline; Coronary Circulation; Coronary Disease; Epinephrine; Methionine; Pharmacology; Poultry; Rabbits; Research; Vasodilator Agents; Vasopressins

Topics: Arginine Vasopressin; Catecholamines; Coronary Disease; Guanethidine; Hypoxia; Metabolism; Norepinephrine; Pharmacology; Phenelzine; Pituitary Hormones, Posterior; Rats; Research; Reserpine; Vasopressins