Depressed baroreflex sensitivity in patients with Alzheimer's and Parkinson's disease.

Parkinson's disease (PD) and Alzheimer's dementia (AD) are often associated with an autonomic neuropathy. The extent of autonomic involvement, however is poorly defined and unpredictable. In order to assess the autonomic cardiovascular regulation baroreflex sensitivity (BRS) was determined non-invasively in 23 patients (age: 65 +/- 9.3 years) with PD and 24 patients with AD (age: 72.3 +/- 7.2 years). The results were compared with those on 22 healthy age- and sex-matched volunteers. Patients with PD and AD exhibited marked abnormalities in cardiovascular autonomic reflex regulation showed by markedly depressed BRS. The possible predictive value of centrally based depression of baroreflex sensitivity necessitates further studies.

Differential efficacy of vasodilators in hypercholesterolaemic rabbits.

The effects of hypercholesterolaemia on the endothelium-dependent and -independent vascular reactivity of the superior mesenteric artery has been examined in anaesthetized rabbits in-vivo. Rabbits were fed with either standard or cholesterol-enriched diet for 24 weeks. Plasma lipids and changes in the endothelin content of plasma and vascular tissue were measured in the superior mesenteric artery and in the thoracic aorta. The functional severity of atherosclerosis was determined by examining vascular responses in the isolated thoracic aorta. The blood flow in the superior mesenteric artery was measured by transit-time flowmetry and drugs were injected through an intra-abdominal aortic catheter. Acetylcholine (5, 10, 20 microg kg(-1)) elicited dose-dependent, mesenteric vasodilation in normocholesterolaemic rabbits. In hypercholesterolaemic animals the response to acetylcholine was completely abolished and even became a vasoconstriction. Endothelin levels in plasma and in the vascular tissue were significantly elevated in hypercholesterolaemic animals compared with controls. Cromakalim at a dose of 3 microg kg(-1), elicited similar mesenteric vasodilation in hypercholesterolaemic and normocholesterolaemic animals. These experiments show that the endothelium-dependent responses of the superior mesenteric artery to acetylcholine are functionally impaired by prolonged hypercholesterolaemia, that this altered vascular reactivity is associated with the elevation of endothelin levels in the circulation and in vascular tissues, and that in hypercholesterolaemia the mesenteric vasodilator effect of the K+-channel opener cromakalim is entirely preserved, suggesting that severe hypercholesterolaemia does not depress the function of ATP-sensitive potassium channels in mesenteric vascular smooth muscle.

The effect of long-term oral captopril treatment on mesenteric blood flow in spontaneously hypertensive rats.

We examined the possibility that changes of the mesenteric resistance play a role in the development of hypertension in spontaneously hypertensive rats (SHRs). Genetically hypertensive (Okamoto) and normotensive Wistar rats (WKYs) were studied after oral treatment for 6 weeks with 100 mg of captopril dissolved in 500 ml water daily. The paired control groups received water. During this treatment, the systolic blood pressure was measured non-invasively with a W+W/BP recorder after preheating of the conscious animals. After these procedures, the rats were anaesthetized, the baseline mesenteric blood flow (MBF, volts) was recorded with a pulsed Doppler flow-meter and the mean arterial blood pressure (MAP) heart rate and mesenteric vascular resistance were also measured. The captopril treatment failed to alter the body weight of SHRs and WKY. In the normotensive group, the MAP was not altered, but the MBF was moderately increased. In contrast, the MAP of the SHRs was markedly decreased, and the MBF was significantly increased. The basal MBF of the SHRs was significantly lower than that of the WKYs. These data suggest that the renin-angiotensin system may exert a tonic vasoconstrictor action on the mesenteric vasculature in SHRs. The increased mesenteric vascular resistance therefore plays an important role in the increased total peripheral resistance in the development of hypertension in SHRs.

[Prostatic cancer metastasized into the kidney and kidney cancer metastasized into the lung]. / Prostatarák áttéte veserákban és ennek tüdömetastasisában.

In a 81-years old man synchronous triple cancers (prostate, kidney and lung) were found at autopsy. The poorly differentiated prostatic adenocarcinoma metastasized to the clear cell carcinoma of the right kidney and to its solitary lung metastasis. The "neoplasm to neoplasm" metastasis and the "metastasis in metastasis" was confirmed by immunohistochemistry.

Capsaicin-sensitive nerves are involved in bile-oleate-induced intestinal hyperemia.

The purpose of the present study is to assess the role of capsaicin-sensitive afferent nerves of the gut in bile-oleate-induced intestinal hyperemia. In anesthetized rats, intestinal blood flow (BF) was determined with a pulsed Doppler flowmeter. Systemic arterial blood pressure and heart rate were also measured. Test solutions containing either 40 or 80 mM oleic acid, combined with 10% natural bile, were introduced into the jejunum and produced abrupt increases in BF (64 +/- 12 and 118 +/- 14% of control, respectively). The vasodilator response was abolished by pretreatment with systemic capsaicin in neonatal life and by topical application of either capsaicin or lidocaine to the mucosa in adult animals. The response was inhibited 69 +/- 6% by an antiserum to vasoactive intestinal peptide. We found no significant inhibition of the vasodilator response by pretreating animals with antisera to cholecystokinin octapeptide or substance P, nor with hexamethonium, atropine, or reserpine. It appears that bile-oleate-induced intestinal vasodilation involves primary afferent nerve fibers of gut that release vasoactive intestinal peptide.

Naphthoherniarin: an unusual coumarin derivative from Ruta graveolens.

The roots of RUTA GRAVEOLENS L. afforded the coumarin derivative, 7-methoxy-6-(5,8-dioxo-7-methoxy-3-methyl-5,8-dihydronaphthalen-1-yl)-chromen-2-one, named naphthoherniarin. The structure was elucidated by spectroscopic methods.

Substance P mediates a gastrointestinal thermoreflex in rats.

We have characterized a viscerocirculatory thermoreflex, quantified its responses, and identified the major neurotransmitter. Application of fluid at 45 degrees C to mucosas or serosas of the stomach, jejunum, or ileum of anesthetized rats promptly evoked consistent cardiovascular responses, namely arterial hypotension, tachycardia, and a diminished intestinal blood flow (latency less than or equal to 5 s with a duration of 2-4 min). Thus, for example, warming of the stomach caused blood pressure to decrease 40%, heart rate to increase 15%, and mesenteric blood flow to decline 50%. These responses were inhibited totally or mostly by capsaicin, administered neonatally, topically, or perineurally, by topical lidocaine, and by parenteral administration of substance P antiserum, somatostatin, or hexamethonium. Epidural anesthesia also inhibited the cardiovascular responses to visceral warming. Pretreatment with reserpine or splanchnic ganglionectomy converted the thermally induced decline in mesenteric blood flow into a vasodilator response, which could then be blocked by an antiserum to substance P. Visceral warming also stimulated afferent, preganglionic sympathetic neural activity. Our conclusions are (a) application of fluid at 45 degrees C to gastrointestinal organs of anesthetized rats initiates a viscerocirculatory reflex that involves primary sensory, afferent C fibers; (b) the major neurotransmitter of this reflex appears to be substance P; and (c) visceral afferent C fibers have central and peripheral vasomotor functions.

Mechanism of "substance P": on mesenteric blood flow; interactions with opioid peptides.

The effects of close intra arterial injection of substance P (SP) and the interaction of SP with opioid peptides, have been studied on mesenteric blood flow in the anaesthetized dog. Injection of SP into the superior mesenteric artery caused a dose dependent increase in mesenteric blood flow. This effect was enhanced by pretreatment with the alpha 2 adrenergic antagonist yohimbine. The action of SP was significantly reduced by pretreatment with muscarinic and nicotinic cholinergic, dopamine and histamine (H1) receptor antagonists. Beta adrenergic, histamine (H2) and opiate receptor antagonists did not influence the action of SP. Pretreatment with tetrodotoxin partially inhibited the effect of SP, indicating that as well as a neurogenic action, it has a direct action on the vascular smooth muscle. The effect of SP was enhanced by D-Met2-NleS5-enkephalinamide, a delta opiate receptor agonist. The actions of D-Met2-NleS5-enkephalinamide were abolished by pretreatment with hexamethonium, partially abolished by naloxone but were unaffected by atropine. The mu opiate receptor agonist, D-Met2-Pro5-enkephalinamide, inhibited the effects of SP.

Evidence for a role of capsaicin-sensitive mucosal afferent nerves in the regulation of mesenteric blood flow in the dog.

Capsaicin injected into the lumen of the small intestine produced marked changes in mesenteric blood flow in anesthetized dogs. In the majority of cases capsaicin evoked a significant increase in mesenteric blood flow, the time-course of which indicated it was of a reflex nature. The response to capsaicin was completely abolished by a previous intraluminal application of the local anesthetic lidocaine, and was inhibited by an intraarterial injection of somatostatin. The present findings suggest that the effects of capsaicin may be related to a release of vasoactive peptides from afferent nerves associated with the vascular system of the gastrointestinal tract. It is concluded that capsaicin-sensitive mucosal afferent nerves, possibly provided with an axon reflex arrangement, may play a role in the regulation of local intestinal blood flow.

Use of immunoblockade to study the involvement of peptidergic afferent nerves in the intestinal vasodilatory response to capsaicin in the dog.

Capsaicin evokes intestinal vasodilatation when given by close arterial injection probably by acting on primary sensory neurons. Several peptides known to occur in primary afferents also have vasodilator effects. We have used immunoblockade to test the hypothesis that the vasodilator effect of capsaicin was mediated by release of these peptides. Antisera to substance P, cholecystokinin, vasoactive intestinal peptide and somatostatin inhibited specifically and dose dependently the effect of each of these peptides given alone. Graded doses of the antisera to substance P, cholecystokinin and vasoactive intestinal peptide also produced a dose dependent inhibition of the vasodilator response to capsaicin. In contrast, administration of somatostatin antiserum enhanced the vasodilator action of capsaicin. Prior administration of antibodies to substance P, cholecystokinin and vasoactive intestinal peptide produced an 80% inhibition of the response to capsaicin. In the presence of these antibodies, and of atropine, the response to capsaicin was reduced by more than 90%. The results suggest that capsaicin increases mesenteric blood flow due to release of substance P, cholecystokinin and vasoactive intestinal peptide. The precise cellular origins of these peptides is unknown, but they may well be released from the peripheral endings of primary afferent neurons.

Mechanism of action of cholecystokinin on intestinal blood flow; interactions with opioid peptides and vasoactive intestinal peptide.

The effects of local administration of CCK-OP on mesenteric blood flow was studied in anaesthetized dogs using an electromagnetic flowmeter and interactions with the opioid peptides and VIP examined. CCK-OP was found to enhance enteral blood flow and tissue metabolism. Investigations with pharmacological antagonists showed that the vasoregulatory effect was exerted neurogenically, by influencing the activities of sympathetic alpha 2 adrenergic, dopaminergic, cholinergic, muscarinergic and nicotinic neurones. The flow-increasing action of CCK-OP was enhanced by D-Met2-NleS5-enkephalinamide; the effect was additive and partially blocked by naloxone. D-Met2-Pro5-enkephalinamide blocked the increases caused by CCK-OP in blood flow and tissue acetylcholine levels. The blockade was not competitive and could be totally eliminated by naloxone. VIP blocked the flow-increasing effect of CCK-OP by a non-competitive mechanism. The results provide data on the peptidergic regulatory mechanisms of the mesenteric circulation.

Relief of mitral incompetence by selective intracoronary thrombolysis in hyperacute myocardial infarction.

Left ventriculography and coronary arteriography were performed in 47 patients with hyperacute myocardial infarction prior to recanalization of the infarct-related vessel. Mitral regurgitation was found in ten patients. After successful recanalization, left ventriculography was repeated in eight of the ten patients with mitral incompetence, and the mitral regurgitation had disappeared in seven. Selective intracoronary thrombolysis resulted in improved left ventricular function and disappearance of mitral incompetence.

Possible involvement of capsaicin-sensitive sensory nerves in the regulation of intestinal blood flow in the dog.

The effect of capsaicin injected into the superior mesenteric artery has been studied on the intestinal blood flow in dogs. Capsaicin evoked a marked dose-dependent increase in mesenterial blood flow in the dose range of 0.1-7 micrograms/kg. The intestinal vasodilatatory effect of capsaicin could invariably be demonstrated after pretreatment with adrenoceptor and dopamine receptor antagonists, as well as with the ganglion blocking agent hexamethonium. Pretreatment with atropine significantly reduced, but did not abolish the increase in intestinal blood flow elicited by capsaicin. Concomitant administration of somatostatin significantly inhibited both the atropine-sensitive and the atropine-resistant components of the effect of capsaicin injected into the superior mesenteric artery. Our results indirectly support the assumption that the intestinal vasodilatatory effect of capsaicin may be mediated by substance P release from capsaicin-sensitive paravascular nerve fibres associated with the blood vessels of the gastrointestinal tract. It is suggested that sensory substance P-containing nerve fibres may be involved in the regulation of the vascular reactions of the gut.

Combined use of selective intracoronary thrombolysis and percutaneous transluminal coronary angioplasty for the treatment of coronary obstruction.

The case of a young female patient with inferior infarction is presented. In the fifth hour after the onset of MI coronary angiography revealed complete obstruction of the right coronary artery. This obstruction has been recanalized by selective intracoronary infusion of streptokinase. At the site of occlusion there remained a 90% coronary stenosis, causing anginal attacks. By means of balloon-catheter angioplasty the stenosis was reduced to less than 50%. The coronary angioplasty resulted in an improvement of left ventricular function, physical working capacity and cessation of anginal attacks.