Perfused Rat Mesentery Research Articles

Pharmacological Features of the Vasodilation Induced by Tertatolol in Isolated Perfused Rat Kidneys

The aim of the studies summarized in the present review was to obtain a pharmacological characterization of the in vitro renal vasodilator action of tertatolol. In isolated Tyrode-perfused rat kidneys, previously constricted with norepinephrine, serotonin or BaCl2, tertatolol evokes vasodilatation. These dilator responses cannot be explained by an interaction of tertatolol with alpha- or beta-adrenoceptors, muscarinic or nicotinic receptors, opioid receptors, dopamine receptors or histamine receptors, and they occur independently of the release of prostaglandins. Since methylene blue, an inhibitor of the soluble form of guanylate cyclase, reduces the renal dilator effect of tertatolol, this action could ultimately depend, at least in part, on the production of cyclic guanosine monophosphate; in this respect, the renal effects of tertatolol and atrial natriuretic factor (ANF) are different. From experiments performed with canine renal arteries and with the perfused rat mesentery, it can be concluded that the effect of tertatolol is more pronounced at the level of the resistance vessels. The in vitro renal dilator response observed with tertatolol may help to explain the beneficial effect on the renal circulation observed in both humans and experimental animals treated with the compound.

The anti-oestrogen tamoxifen is a calcium antagonist in perfused rat mesentery.

The anti-oestrogen tamoxifen in the range 10(-7)-10(-5) M induced concentration-related inhibition of potassium-stimulated vasospasm in the isolated perfused rat mesentery vascular bed. In contrast, responses to noradrenaline did not fall below control levels until the tamoxifen concentration exceeded 4 X 10(-6) M. Recovery of the potassium-stimulated responses was also concentration-related. The most likely explanation is that while tamoxifen can obstruct the entry of extracellular calcium, it is unable to prevent the intracellular release of the ion by noradrenaline.

Chemical renal medullectomy prevents frusemide-induced inhibition of sympathetic vasoconstriction in the in situ blood perfused rat mesentery.

The mesentery of anaesthetized rats was perfused in situ at a constant rate, via the cannulated superior mesenteric artery, with blood drawn from a cannulated carotid artery. Increases in perfusion pressure were produced by peri-arterial electrical stimulation of the mesenteric sympathetic nerves at 3, 6 and 10 Hz before and after the intravenous administration of frusemide 5 mg/kg. Loss of solutes and volume as a result of frusemide-induced diuresis was prevented by a urinary bladder-venous shunt. In control animals the vasoconstrictor responses to mesenteric nerve stimulation were significantly reduced after frusemide administration. However, in animals pretreated 4 weeks previously with bromethylamine (BEA) 200 mg/kg i.p., frusemide had no effect on vasoconstrictor responses. Chemical papillectomy with BEA has been shown by others to prevent the antihypertensive effects attributed to the non-prostanoid lipids produced by the interstitial cells of the renal medulla. Our data suggest that the vasoconstrictor-inhibiting effect of frusemide may be mediated by the release of renomedullary lipids.

An isolated perfused rat mesentery model for direct observation of the vasculature during cryopreservation

An intact vasculature is essential for successful hypothermic perfusion and cryopreservation of solid organs, but few studies have specifically assessed the vascular effects of these procedures. A technique was therefore developed for continuous, direct observation of an isolated vascular bed during hypothermic perfusion with cryoprotectants, and during freezing and thawing. The isolated rat mesentery was spread across a controlled low temperature microscope stage and perfused with solutions containing fluorescein isothiocyanate (FITC)-Dextran 70 as an indicator of macromolecular permeability of the vessels. Hypertonic citrate washout, HP-5 perfusion (23), rapid and slow addition and removal of glycerol, and freezing/thawing were studied. Control perfusion with HP-5 produced slow FITC-Dextran leakage, reflecting normal physiological macromolecular permeability of vessels. Rapid addition of glycerol dramatically increased vascular permeability, consistent with osmotic damage to vessels. Rapid removal stopped flow through capillaries and decreased vascular dimensions, suggesting overhydration of endothelial cells and extravascular tissue. Venules and capillaries were the most susceptible vessels to osmotic stress. Slow addition and removal of glycerol (80 mmol/ liter/min) produced results similar to control perfusions. During slow freezing (0.5 °C/min to −5 °C) extravascular ice compressing vessels was more obvious than intravascular ice. Glycerol afforded some protection to the microvasculature during freeze/thaw cycles since flow was reestablished in venules and arterioles after thawing, although FITC-Dextran leakage indicated that damage had occurred.

An isolated perfused rat mesentery model for direct observation of the vasculature during cryopreservation

An isolated perfused rat mesentery model for direct observation of the vasculature during cryopreservation

Modulatory effects of substance P on norepinephrine induced vasoconstrictor responses in the rat mesentery

1. 1. The role of substance P (SP) in adrenergic transmission has been studied in the isolated perfused rat mesentery. 2. 2. Intra-arterial perfusion of SP (4 × 10 −9 to 4 × 10 −7 M) produced a dose dependent potentiation of norepinephrine (NE) induced vasoconstrictor responses and a shift of the log dose-response curve to the left. 3. 3. Saralasin, a specific antagonist of angiotensin II (ang. II) when perfused at a concentration of 3 × 10 −9 M did not change the NE responses as such. However, the potentiating effect of SP could not be demonstrated in the presence of saralasin. 4. 4. Indomethacin, a prostaglandin (PG) synthetase inhibitor, when perfused at a concentration of 2.8 × 10 −6 M, markedly attenuated the vascular responses to NE, which could not be normalized by the addition of SP. 5. 5. It appears that SP's potentiating effect on NE responses in the perfused rat mesentery simulates ang. II and not prostaglandins. A direct non-specific post synaptic sensitizing effect of SP on vascular smooth muscle cell, for its potentiating property, cannot be ruled out.

Pharmacological and hemodynamic studies on flunarizine

Systemic administration of flunarizine (3 mg/kg i.v.) to rats decreased the vascular reactivity of their mesenteries to phenylephrine (PhE) and norepinephrine (NE). Intra-arterial perfusion of flunarizine (100 pg to 1 μg/ml) produced dose dependent attenuation of the vasoconstrictor responses induced by PhE and Ne in the isolated perfused rat mesentery. Flunarizine (5 mg/kg i.p.) did not significantly affect general hemodynamics (i.e. mean blood pressure, heart rate, cardiac output and hematocrits) in anaesthetized rats. However, it produced significant decreases in the blood flows to the kidneys and the spleen associated with similar changes in the percentage distribution of the cardiac output to these organs. These studies indicate that in rats, flunarizine produced preferential effects in different vascular beds.

Vasodilation and aging evaluated in the isolated perfused rat mesenteric vascular bed: preliminary observations on the vascular pharmacology of dobutamine.

The influence of animal age of drug-induced vasodilation was investigated in the perfused rat mesentery constricted with norepinephrine. Responses to isoproterenol, a beta-receptor stimulant, decreased with increasing age. Also, there was a modest decline in the relaxation produced by papaverine. In contrast, dilation of the rat mesentery by acetylcholine, histamine, or nitroglycerin either did not change with age or the responses became somewhat larger. Dobutamine, a myocardial beta-receptor stimulant, produced a marked relaxation of the mesentery. A comparison of the action of isoproterenol and dobutamine revealed that isoproterenol stimulated vascular beta-receptors, whereas dobutamine relaxed the mesentery by antagonizing the tone produced by norepinephrine. The dilation resulting from the alpha-receptor-blocking action of dobutamine was unrelated to animal age.

The in situ blood perfused rat mesentery; A model for assessing modulation of adrenergic neurotranmission

The present study describes a method for the in situ blood perfusion of the rat mesentery and compares this method with the in vitro method of McGregor. The in situ method gives stable baseline perfusion pressures for over 2 h and consistent vasoconstrictor responses to both periarterial nerve stimulation (NS) and exogenous norepinephrine (NE). The responses to NS are blocked by phentolamine and reserpine whereas the responses to NE are blocked by phentolamine but potentiated by reserpine. The threshold responses to NS and NE were 3 Hz and 100 ng, respectively, in the in situ preparation and 11 Hz and 200 ng, respectively, in the in vitro preparation. When the effects of prostaglandin E 2 (PGE 2) were examined in indomethacin-treated mesenteries, PGE 2 decreased the responses to both NS and NE in the in situ preparation, but in the in vitro preparation, PGE 2 enhanced the response to NS and NE. Thus, the in situ blood perfused rat mesentery is a stable and reproducible model for examining the effects of drugs and hormones on adrenergic neurotransmission and responses to exogenous norepinephrine.

Inhibition of neuronal noradrenaline uptake by angiotensin II in the rat mesentery

In the isolated perfused rat mesentery, angiotensin II (3 × 10−9 M) in subpressor doses enhanced the vasoconstrictor responses to noradrenaline by 9.6 ± 1.4 mmHg. However, in mesenteries obtained from rats chemically sympathectomized with 6-hydroxydopamine, angiotensin II was without effect. Treatment of mesenteries with the noradrenaline neuronal uptake blockers desmethylimipramine (10−10 M), protriptyline (10−10 M), or cocaine (10−6 M) potentiated responses to noradrenaline by 3.8 ± 0.84, 3.7 ± 0.67, and 5.5 ± 0.26 mmHg, respectively. Angiotensin II alone or in combination with either desmethylimipramine, protriptyline, or cocaine potentiated the noradrenaline responses to a similar extent. On the other hand, corticosterone (1.5 × 10−6 M), an extraneuronal uptake blocker, enhanced noradrenaline responses by 4.3 ± 1.4 mmHg, and this enhancement was additive with the potentiation produced by cocaine and (or) angiotensin II. We conclude that angiotensin II in subpressor doses acts presynaptically to block selectively the neuronal uptake of noradrenaline without any appreciable effect on extraneuronal uptake.

Modulation of adrenergic transmission by angiotensins in the perfused rat mesentery

Isolated rat mesenteric arteries perfused with a modified Krebs solution were utilized to study the effects of angiotensin II (AII), angiotensin III (AIII), and [des-Asp1-Arg2]AII on adrenergic transmission. Angiotensin II potentiated vasoconstrictor responses to both sympathetic nerve stimulation and to exogenous norepinephrine, whereas AIII and [des-Asp1-Arg2]AII potentiated vasoconstrictor responses to exogenous norepinephrine only. When the responses to exogenous norepinephrine were compared, the order of agonist potency was AIII greater than AII greater than [des-Asp1-Arg2]AII. The potentiation of sympathetic nerve stimulation by AII was inhibited by simultaneous administration of AIII (25%), [des-Asp1-Arg2]AII (51%), [Sar1-Ile8]AII (83%), and (Ile7)AIII (80%). The potentiation of exogenous norepinephrine by AII, AIII, and [des-Asp1-Arg2]AII was inhibited by [Sar1-Ile8]AII (110%, 113%, and 108%, respectively) and by [Ile7]AIII (50%, 64%, 91%, respectively). We conclude that AII possesses the capacity both to increase norpinephrine release during sympathetic nerve stimulation and to decrease norepinephrine reuptake, whereas AIII and [des-Asp1-Arg2]AII decrease norepinephrine release and reuptake. Also, under conditions of increased N-terminal degradation of AII, blockade of norepinephrine reuptake would be increased while the release of norepinephrine by nerve stimulation would be reduced.

The effects of prostaglandin perfusion on the vascular responses to nerve stimulation and sympathomimetic amines

(1) The effects of prostaglandins E1, E2 and F2α on the responses of the perfused rat mesentery to nerve stimulation and sympathomimetic amines were investigated. (2) PGE1, E2 and F2α inhibited responses to sympathetic nerve stimulation maximally at a perfusion concentration of 10 mg ml−1. Responses to tyramine, octopamine, noradrenaline and metaraminol were inhibited maximally at a concentration of 100 ng ml−1. (3) The most potent inhibitor was PGE1, and the greatest percentage inhibition (67%) was in the presence of tyramine. (4) Indomethacin had no effect on responses to sympathomimetic amines. (5) It was concluded that PGs have a role in the release of noradrenaline by nerve stimulation and by sympathomimetic amines.

Effects of ganglionic blocking agents on adrenergic transmission in rat mesenteric arteries.

ARTICLESEffects of ganglionic blocking agents on adrenergic transmission in rat mesenteric arteriesKU Malik, and JC McGiffKU Malik, and JC McGiffPublished Online:01 Nov 1972https://doi.org/10.1152/ajplegacy.1972.223.5.1210MoreSectionsPDF (1 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByEffects of Intraperitoneal Captopril on Peritoneal Transport in Rats24 February 2020 | Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis, Vol. 7, No. 2The in situ blood perfused rat mesentery; A model for assessing modulation of adrenergic neurotranmissionEuropean Journal of Pharmacology, Vol. 66, No. 2-3THE FUNCTION OF ACETYLCHOLINE RELEASED FROM SYMPATHETIC FIBRESClinical and Experimental Pharmacology and Physiology, Vol. 4, No. 1Facilitation of adrenergic transmission by locally generated angiotensin II in rat mesenteric arteries.Circulation Research, Vol. 38, No. 1Relationship of Glucose Metabolism to Adrenergic Transmission in Rat Mesenteric ArteriesCirculation Research, Vol. 35, No. 4Prostaglandins and the KidneyCirculation Research, Vol. 33, No. 5 More from this issue > Volume 223Issue 5November 1972Pages 1210-1215 Copyright & PermissionsCopyright © 1972 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1972.223.5.1210PubMed4347445History Published online 1 November 1972 Published in print 1 November 1972 Metrics