Mechanisms of acetylcholine-induced relaxation in dog external and internal ophthalmic arteries.

Mechanisms underlying the relaxant response to acetylcholine (ACh) were examined in dog external (EOA) and internal ophthalmic arteries (IOA). Acetylcholine produced relaxation in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha. The relaxations induced by ACh in these arteries were not inhibited by endothelium denudation.

Monkey cerebral arterial relaxation caused by hypercapnic acidosis and hypertonic bicarbonate.

In helical strips of Japanese monkey cerebral arteries contracted with vasoconstrictors, applications of high CO2 (15% compared with 5% CO2 in control media) and hypertonic NaHCO3 (50 mM) produced relaxations. Similar relaxations were also obtained in human cerebral arterial strips. Hypercapnia increased PCO2 and resulted in acidosis in the bathing media, and the addition of NaHCO3 restored the pH to normal with high PCO2 and increased the osmotic pressure.

Nitric oxide-mediated retinal arteriolar and arterial dilatation induced by substance P.

Purpose: The present study was undertaken to compare vasodilatations caused by substance P in retinal arterioles in vivo and in the extraocular retinal central arteries in vitro, and to analyze the mechanisms of its action.

Methods: In the in vivo study, changes of the retinal arteriolar diameter were continuously measured using a retinal fundus camera. In the in vitro study, changes in the isometric tension were recorded in helical strips of extraocular retinal arteries with and without the endothelium, exposed to aerated bathing media.

Neural mechanism underlying basilar arterial constriction by intracisternal L-NNA in anesthetized dogs.

Basilar arterial diameters were angiographically measured in anesthetized dogs in which systemic blood pressure and heart rate were also monitored. Injections of NG-nitro-L-arginine (L-NNA), a NO synthase inhibitor, into the cisterna magna produced a significant, persistent decrease in arterial diameter, the effect being reversed by intracisternal injections of L-arginine. The vasoconstrictor effect of L-NNA was diminished in dogs treated with hexamethonium.

Interactions of nitrovasodilators and atrial natriuretic peptide in isolated dog coronary arteries.

In helical strips of dog coronary arteries contracted with prostaglandin F2 alpha, relaxant responses to atrial natriuretic peptide (ANP), nitric oxide (NO), nitroglycerin and 8-bromo cyclic GMP were markedly inhibited or abolished by treatment with a high concentration of sodium nitroprusside, whereas the responses to beraprost and papaverine were not influenced. A similar suppression of the responses to ANP, NO, and sodium nitroprusside was observed after treatment with nitroglycerin. The relaxations induced by NO and nitroglycerin were abolished by methylene blue and oxyhemoglobin, whereas the response to ANP was not influenced.

Nitric oxide mediates, and acetylcholine modulates, neurally induced relaxation of bovine cerebral arteries.

Helical strips of bovine basilar arteries denuded of the endothelium responded to transmural electrical stimulation with frequency-dependent relaxations that were abolished or markedly attenuated by treatment with tetrodotoxin, oxyhemoglobin and Methylene Blue. Relaxations induced by vasoactive intestinal polypeptide and calcitonin gene-related peptide were not affected by oxyhemoglobin and Methylene Blue. The neurally induced relaxation was not attenuated in the artery made unresponsive to these peptides by successive application.

[Hypervitaminosis D].

Excessive vitamin D causes marked and prolonged hypercalcemia by accelerating intestinal calcium absorption and bone resorption. Vitamin D induced hypercalcemia includes the toxic ingestion of excessive amount of vitamin D preparations, granulomatous diseases and lymphoproliferative malignancies. In vitamin D toxicity, the clinical courses vary depending on the vitamin D preparation responsible for the hypercalcemia.

Cerebroarterial relaxations mediated by nitric oxide derived from endothelium and vasodilator nerve.

Purposes of this study were to determine whether: (1) nitric oxide is involved in endothelium-dependent relaxation in helical strips of dog cerebral arteries; (2) relaxing factor distinct from NO is also involved, and (3) susceptibility to NG-nitro-L-arginine (L-NA), an NO synthase inhibitor, of the response to mediators liberating NO from the endothelium and nerve differs. Changes in isometric tension were recorded. In the strips contracted with prostaglandin F2 alpha, substance P and arginine vasopressin produced a relaxation which was abolished or reversed to a contraction by endothelium denudation.

Potentiation by hypoxia of contractions caused by angiotensin II in dog and monkey cerebral arteries.

Background And Purpose: Hypoxia alters the responsiveness to endogenous substances of cerebral arteries, possibly resulting in the modulation of blood supply to ischemic brain regions. The present study was undertaken to analyze the mechanism of potentiation by hypoxia of angiotensin II-induced cerebroarterial contractions.

Methods: Monkey and dog cerebral arterial strips with endothelium were suspended for isometric tension recording in Ringer-Locke solution aerated with 95% O2-5% CO2 (partial pressure, 570-600 mm Hg) or 95% N2-5% CO2 (approximately 10 mm Hg).

Cerebral vasoconstrictor mediators.

Endogenous cerebral vasoconstrictor mediators regulate vascular resistance and blood flow in the brain as a whole and in various regions and participate in the pathogenesis of cerebral circulatory disturbances. Vasoconstrictors are effective in the treatment of diseases associated with cerebral vasodilatation. There are variations in the response of cerebral arteries from primate and subprimate mammals; therefore, information as to similarities and differences in their response is quite important in evaluating the physiological role, involvement in pathogenesis and therapeutic usefulness of the mediators in healthy men and patients.

Mechanisms of endothelium-dependent responses to vasoactive agents in isolated porcine coronary arteries.

In isolated porcine coronary arteries, acetylcholine elicited contractions that were potentiated by endothelium denudation. In endothelium-intact strips, the contraction deteriorated by repeated trials and was reversed to a relaxation. NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthesis inhibitor, abolished the relaxation or reversed it to a contraction.

Mediation by nitric oxide of neurally-induced human cerebral artery relaxation.

Human cerebral artery strips relaxed in response to non-adrenergic, non-cholinergic vasodilator nerve stimulation by electrical pulses or nicotine. The relaxation response was abolished by treatment with NG-nitro-L-arginine, a nitric oxide synthase inhibitor; the inhibitory effect was reversed by L-, but not D-, arginine. Nitric oxide-induced relaxation was unaffected.

Cerebello- and pallido-thalamic pathways to areas 6 and 4 in the monkey.

Projections from the cerebellar nuclei (CN) and the internal segment of the globus pallidus (GPi) to areas 6 and 4 via the thalamus were examined electrophysiologically in monkeys. In addition to the well-known pallido-thalamo-cortical projection to area 6, some thalamic neurons with CN input were found to project to area 6. Seventeen neurons in VLc, area X and the dorsal margin of VPLo were activated antidromically by stimulation of supplementary motor or premotor areas, and orthodromically by CN stimulation.

Mechanisms of histamine-induced relaxation in external and internal ophthalmic arteries.

Purpose: Mechanisms that underlie the relaxant response to histamine were examined in dog external (a branch of external carotid artery) and internal (a branch of internal carotid artery) ophthalmic arteries (EOA and IOA).

Methods: Changes in isometric tensions were recorded in helical strips of the arteries with and without the endothelium.

Results: Histamine predominantly produced relaxations in EOA and IOA, partially contracted with prostaglandin (PG) F2 alpha.

Impairment by damage of the pterygopalatine ganglion of nitroxidergic vasodilator nerve function in canine cerebral and retinal arteries.

Histochemical study revealed that transcutaneous injection of ethanol into the vicinity of the pterygopalatine ganglion greatly decreased the positive staining for NADPH diaphorase activity after 1 week in the ipsilateral ganglion of a dog and abolished the staining of perivascular nerves in the middle and posterior cerebral arteries. Transmural electrical stimulation or nicotine produced a relaxation in middle and posterior cerebral arteries isolated from the side with the nontreated ganglion (control side), whereas the relaxation was abolished or reversed to a contraction in the arteries from the side with the ethanol-treated ganglion. Nitric oxide-induced relaxations did not differ in the arteries from both sides.

Neural mechanism of hypertension by nitric oxide synthase inhibitor in dogs.

This study aimed to determine the mechanism of hypertension associated with nitric oxide synthase inhibition. Intravenous injections of NG-nitro-L-arginine, a nitric oxide synthase inhibitor, produced a sustained increase in systemic blood pressure and a decrease in heart rate in anesthetized dogs, whereas NG-nitro-D-arginine had no effect. L-Arginine reversed the pressor response.

Mechanisms of the biphasic responses to endothelin-3 in dog coronary arteries.

1. Endothelin-3 (ET-3) elicited relaxations at low concentrations (up to 10(-8) M) and contractions at higher concentrations in dog isolated coronary arteries precontracted with prostaglandin F2 alpha (PGF2 alpha). The relaxation by ET-3 was not affected by endothelium denudation nor treatment with NG-nitro-L-arginine, but was abolished or reversed to a contraction by treatment with indomethacin and markedly suppressed by tranylcypromine, a PGI2 synthetase inhibitor, or diphloretin phosphate, a prostaglandin receptor antagonist.

Involvement of nitric oxide in endothelium-dependent, phasic relaxation caused by histamine in monkey cerebral arteries.

Monkey cerebral artery strips partially contracted with prostaglandin F2 alpha responded to histamine with biphasic patterns of relaxation. The delayed and sustained relaxation was suppressed by cimetidine, whereas the phasic response was abolished by treatment with chlorpheniramine and NG-nitro-L-arginine (L-NA), a nitric oxide (NO) synthase inhibitor. The inhibition by L-NA was reversed by L-arginine.

Mechanisms of relaxation induced by prostaglandins in isolated canine uterine arteries.

Objective: Prostaglandins liberated from the uterus in response to chemical and physical stimuli would be important modulators of uterine arterial tone and blood flow. This study was aimed at analyzing mechanisms of vasodilator action of prostaglandins in uterine arteries.

Study Design: Canine uterine artery strips were suspended in Ringer-Locke solutions for isometric tension recording.

Local generation and action of angiotensin II in dog iris sphincter muscle.

Existence of the renin-angiotensin system was pharmacologically investigated in the dog isolated iris sphincter muscle. The sphincter muscle contracted in response to tetradecapeptide, a synthetic renin substrate, angiotensin (ANG) I and ANG II dose-dependently. The contractions induced by these peptides were suppressed by treatment with saralasin, indomethacin and aspirin.

AE0047, a new dihydropyridine Ca2+ entry blocker, inhibits the responses to adrenergic nerve stimulation and substance P in dog mesenteric arteries.

AE0047, a new dihydropyridine-type Ca2+ entry blocker, significantly inhibited the contractions induced by transmural electrical stimulation and norepinephrine in dog mesenteric artery strips. The inhibition was greater in the case of the response to nerve stimulation. The 3H-overflow ratio evoked by electrical stimulation from strips previously soaked in [3H]norepinephrine was significantly reduced by AE0047 but not by nicardipine in a concentration sufficient to attenuate the response to norepinephrine.

[Neurotransmission and nitric oxide (NO)].

The history of how we reached the goal of determining the mechanism of vasodilatation caused by non-adrenergic, non-cholinergic nerve stimulation in cerebral arteries was traced. We concluded from this project that electrical and chemical (by nicotine) stimulations evoke an increased influx of Ca2+ into nerve terminals and activate nitric oxide (NO) synthase, resulting in the synthesis and release of NO that stimulates the guanylate cyclase in smooth muscle, thereby causing the accumulation of cyclic GMP and eliciting muscle relaxation. Reviewed also are the neurally-induced inhibitory responses of extracranial arteries, intestines, etc.

Regional difference in the response mediated by beta 1-adrenoceptor subtype in bovine cerebral arteries.

Helical strips of bovine rostral cerebral arteries (anterior cerebral, middle cerebral, and internal carotid artery) responded to norepinephrine with contractions, whereas the caudal cerebral arteries (posterior communicating, posterior cerebral, and basilar artery) relaxed in response to the amine. After blockade of alpha-adrenoceptors, norepinephrine-induced rostral artery contractions were reversed to relaxations, which were smaller than those in the caudal arteries. Isoproterenol, dobutamine, and terbutaline produced greater relaxations in caudal than in rostral arteries, but forskolin relaxed these arteries to a similar magnitude.

Different susceptibility of vasodilator nerve, endothelium and smooth muscle functions to Ca++ antagonists in cerebral arteries.

Effects of selective (nicardipine) and nonselective (Cd++) Ca++ channel antagonists on the responses of isolated dog cerebral arteries to vasodilator nerve stimulation, substance P, serotonin and prostaglandin F2 alpha were investigated; the relaxation caused by the nerve stimulation and the peptide is mediated by NO, possibly from the nerve and endothelium, respectively. Relaxant responses to nerve stimulation by electrical pulses and nicotine in the endothelium-denuded arteries were attenuated by Cd++, but not influenced by nicardipine; the concentrations of these antagonists were sufficient to suppress contractions caused by prostaglandin F2 alpha and serotonin to a similar extent. Increase in cyclic GMP by nicotine was also suppressed solely by Cd++.