Biomedical subjects

G J Smits

Publications and source records attributed to G J Smits.

At least 37 records · Page 2Linked to original sources

PubMed1994

Tachykinin receptors involved in the contractile effect of the natural tachykinins in the rat gastric fundus.

1. The receptors involved in mammalian tachykinin-induced contractions of longitudinal smooth muscle strips of the rat gastric fundus were characterized pharmacologically. 2. Substance P (SP), neurokinin A, neurokinin B and senktide contracted the strips in a concentration-dependent manner with a potency order of neurokinin A > or = senktide > neurokinin B > substance P. The contractions were not influenced by tetrodotoxin and atropine. 3. L 659877, a NK2B-receptor-preferring antagonist reduced neurokinin A- and neurokinin B-induced contractions (estimated pKB 6.9 and 6.3, respectively) but had less pronounced effects on SP-induced contractions and none on contractions induced by senktide. MEN 10376, an NK2A-receptor-preferring antagonist, reduced the neurokinin A-induced contractions (estimated pKB 5.2), while dactinomycin, reduced the neurokinin A-induced contractions only to a minor extent at 10(-4) M. 4. CP 96345, an NK 1-receptor antagonist, reduced substance P- and neurokinin A-induced responses, but also reduced the contractions induced by KCl and methacholine. RP 67580, another non-peptide NK1-receptor antagonist had no effect on the substance P-, neurokinin A- and neurokinin B-induced contractions up to a concentration of 3 x 10(-6) M. 5. These results suggest that the mammalian tachykinins induce contractions of the longitudinal smooth muscle strip of the rat gastric fundus by direct action at muscular NK2B- and NK3-receptors.

Animals↗

PubMed1993

Synthesis and structure-activity relationships of nonpeptide, potent triazolone-based angiotensin II receptor antagonists.

2,5-Dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4' - yl]methyl]-3H-1,2,4-triazol-3-one, SC-51316, was synthesized as a potent and orally active angiotensin II (AII) receptor antagonist with a long duration of action. To explore the lipophilic pocket in the AII receptor interacting with the substituent at the 2-position of triazolone-based antagonists, a series of compounds were prepared and evaluated for receptor binding affinity and antagonism of AII-contracted rabbit aortic rings. It has been found that the pocket is very spacious and can accommodate different sizes of lipophilic groups and various functionalities. Acidic groups generally result in a slight decrease in binding affinity. Branched chains are unfavorable. The freedom of rotation around C2-C3 in the flexible side chain is crucial for good binding. The 2-phenylethyl-substituted triazolone analogue exhibits the highest in vitro potency among all compounds that have been synthesized.

Angiotensin Receptor Antagonists↗

PubMed1993

Nonpeptide angiotensin II antagonists: N-phenyl-1H-pyrrole derivatives are angiotensin II receptor antagonists.

A series of 5-[1-[4-[(4,5-disubstituted-1H-imidazol-1-yl)methyl]- substituted]-1H-pyrrol-2-yl]-1H-tetrazoles and 5-[1-[4-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-substituted]- 1H-pyrrol-2-yl]-1H-tetrazoles were investigated as novel AT1-selective angiotensin II receptor antagonists. Computer-assisted modeling techniques were used to evaluate structural parameters in comparison to the related biphenyl system. New synthetic procedures have been developed to prepare the novel compounds. The best antagonists in this series had IC50 values (rat uterine membrane receptor binding) in the 10(-8) M range and corresponding pA2 in isolated organ assay (rabbit aorta rings). Structure-activity relationships indicate some similarities with the finding in the biphenyl system. Substitution on the pyrrole ring modulates activity. Compound 5 antagonized angiotensin-induced blood pressure increase when administered to conscious rat at 30 mg/kg per os.

Angiotensin II↗

PubMed1993

In vivo pharmacology of SC-51316, a nonpeptidic angiotensin II receptor antagonist.

The depressor activity of a novel nonpeptidic angiotensin II (AII) receptor antagonist, SC-51316 (2,5-dibutyl-2,4-dihydro-4-[[2-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4 '- yl]-methyl]-3H-1,2,4-triazol-3-one), is described. In anesthetized, ganglion-blocked rats, intravenous administration of SC-51316 inhibited the pressor response to an infusion of AII. To determine antihypertensive efficacy, conscious, spontaneously hypertensive rats were administered SC-51316 (30 mg/kg intragastrically) daily for 5 days. Blood pressure was reduced in a similar manner to that observed with the angiotensin converting enzyme inhibitor enalapril (10 mg/kg intragastrically). SC-51316 had no effect on heart rate. In conscious, sodium-deficient dogs, administration of SC-51316 (30 mg/kg orally) or enalapril (10 mg/kg orally) lowered blood pressure similarly over a 24 h observation period. Thus, SC-51316 antagonizes the activity of AII in vivo and is an orally active, antihypertensive agent.

Angiotensin II↗

PubMed1993

Angiotensin subtype 1 blockade selectively potentiates adenosine subtype 2-mediated vasodilation.

A previous report demonstrated that infusion of adenosine into the forearm increased local vascular production of angiotensin II. We hypothesize that this increase in angiotensin II could attenuate the vasodilator response to adenosine subtype 2 (A2) receptor activation. The depressor and regional hemodynamic responses to the A2-selective adenosine agonist DPMA were measured in the presence and absence of angiotensin subtype 1 (AT1) receptor blockade (losartan, 10 mg/kg IV) in anesthetized rats. Losartan pretreatment (without versus with losartan) significantly potentiated DPMA-induced reductions in renal (-13 +/- 2% versus -22 +/- 4%, P < .05) and mesenteric (-11 +/- 2% versus -23 +/- 4%, P < .05) vascular resistances, resulting in a greater depressor response (-7 +/- 2 versus -18 +/- 3 mm Hg, P < .05). The decrease in hindquarter vascular resistance was not affected. To test the specificity of this interaction, we also evaluated nitroglycerin and nifedipine. Pretreatment with losartan had no effect on the responses to nitroglycerin, whereas the responses to nifedipine either were not affected or were attenuated (percent change in mesenteric vascular resistance: without losartan pretreatment, -30 +/- 1%; with losartan pretreatment, -24 +/- 2%, P < .05). To determine whether the decrease in arterial pressure after losartan pretreatment contributed to the potentiation of the DPMA-mediated effects, we infused nitroglycerin to lower mean arterial pressure comparably to losartan treatment. None of the hemodynamic responses to subsequent DPMA administration were affected. These data suggest that endogenous levels of angiotensin II, whether released locally or systemically, selectively attenuate the A2-mediated reductions in renal and mesenteric vascular resistances.

Adenosine↗

PubMed1993

Pharmacology of SC-52458, an orally active, nonpeptide angiotensin AT1 receptor antagonist.

We describe the pharmacologic properties of SC-52458, 5-[(3,5-dibutyl-1H-1,2,4-triazol-1-yl)methyl]-2-[2-(1H-tetrazol - 5-ylphenyl)]pyridine, a novel nonpeptide angiotensin II (AII) receptor antagonist. SC-52458 was a potent inhibitor of [125I]AII binding to AT1 receptors in rat adrenal cortex and uterine smooth muscle membranes (IC50 values of 2.8 and 6.9 nM, respectively). Contraction of rabbit aortic rings by AII was antagonized by SC-52458 in a competitive and reversible manner (pA2 of 8.18). SC-52458 had no effect on the activity of angiotensin converting enzyme (ACE) or renin in vitro. In normotensive rats, administration of SC-52458, either intravenously (i.v.) or by gavage, inhibited the pressor response to AII. Daily treatment with SC-52458 at 20, 30, and 50 mg/kg by gavage for 4 days decreased blood pressure (BP) in conscious, spontaneously hypertensive rats (SHR). Further studies in renal-artery ligated rats and sodium-deficient dogs demonstrated that oral administration of SC-52458 decreased BP and that this activity was correlated with significant plasma levels of the compound. SC-52458 is an orally active, competitive AT1-receptor antagonist with antihypertensive properties.

Administration, Oral↗

PubMed1993

In vitro and in vivo characterization of an A1-selective adenosine agonist, RG14202.

In this report, we demonstrate that the adenosine agonist N-5'-ethyl-N6-(cyclopentyl) adenosine-5'-uronamide (RG14202) is a vasorelaxant in porcine coronary arterial rings (EC50 = 0.37 +/- 0.054 microM; n = 19). This vasorelaxation (VR) occurs despite RG14202 being 275-fold selective for the rat brain A1 receptor. VR in response to RG14202 was attenuated markedly by the nonselective adenosine antagonist CGS15943, whereas 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), a highly selective A1 antagonist, had only a small inhibitory effect. In contrast, the potassium channel blocker glybenclamide attenuated RG14202-induced VR markedly (85-fold), indicating that modulation of potassium channels is likely involved. In carotid arterial rings, RG14202 was approximately 5 times less potent than in the coronary artery, suggesting that this compound may be more selective for the coronary vasculature. In anesthetized rats, i.v. administration of RG14202 caused a significant decrease in mean arterial pressure only at the highest dose (3 micrograms/kg). In comparison, heart rate was decreased dose-dependently with maximal changes at 3 micrograms/kg. Both the depressor and bradycardic responses could be antagonized with CGS15943. RG14202 increased renal, but had no effect on mesenteric or hindquarter vascular resistance. Glybenclamide pretreatment (20 mg/kg) did not significantly alter the effects of RG14202 on heart rate or regional vascular resistances; however, the depressor response to RG14202 was attenuated.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗

PubMed1992

Influence of age on responsiveness of rat gastric fundus to agonists and to stimulation of intrinsic nerves.

The contractile effect of methacholine, prostaglandin F2 alpha (PGF2 alpha) and electrical stimulation of cholinergic neurones, and the relaxant effect of nitric oxide (NO), vasoactive intestinal polypeptide (VIP) and electrical stimulation of inhibitory non-adrenergic non-cholinergic (NANC) neurones were studied in longitudinal smooth muscle strips of the gastric fundus of young (3 months), adult (12 months) and old (24 months) male Wistar rats. The contractile responses to methacholine and to electrical stimulation of cholinergic neurones were not significantly different between the three age groups. The responses to PGF2 alpha were significantly more pronounced in young than in adult and old rats. The relaxant response to electrical stimulation of NANC neurones with a cumulative increase in frequency showed a decreased response in old rats at the higher stimulation frequencies. This was mimicked by a decreased response to VIP, suggesting that there is a decrease in muscular sensitivity to VIP rather than an impaired capacity to VIP release with increasing age. The relaxant response to electrical stimulation of NANC neurones with short trains was similar in the three age groups, while the sensitivity to exogenous NO increased with age. The latter might be a compensatory mechanism for a decrease in stimulation-induced NO release with age.

Aging↗

PubMed1992

Influence of vasoactive intestinal polypeptide and NG-nitro-L-arginine methyl ester on cholinergic neurotransmission in the rat gastric fundus.

The possible modulating effect of vasoactive intestinal polypeptide (VIP) and nitric oxide (NO), on cholinergic neurotransmission was assessed in longitudinal muscle strips of rat gastric fundus. VIP and NO are the putative co-transmitters of the inhibitory non-adrenergic non-cholinergic (NANC) neurones in this tissue. VIP concentration dependently inhibited cholinergic contractions induced by 2-min transmural stimulation, relaxed tissues, the tone of which was continuously raised by transmural stimulation, and shifted to the right the frequency-response curves for contraction induced by transmural stimulation with a cumulative increase of frequency. The same effect was found when contractions were induced with methacholine, suggesting that only functional antagonism at the postsynaptic smooth muscle cell level is involved. On 30-min incubations, 3 x 10(-4) M NG-nitro-L-arginine methyl ester (L-NAME) potentiated cholinergic responses to 20-s transmural stimulation, while not influencing contractions of similar amplitude evoked by methacholine; the cholinergic responses to 2-min transmural stimulation were also not influenced. The potentiating effect of L-NAME was prevented by L-arginine but not D-arginine. These results suggest that endogenous NO released from the inhibitory NANC neurones during short trains of transmural stimulation interferes with cholinergic neurotransmission either by functional antagonism of acetylcholine at the postsynaptic level or by presynaptic inhibition of acetylcholine release.

Acetylcholine↗

PubMed1992

Modulation of non-adrenergic non-cholinergic inhibitory neurotransmission in rat gastric fundus by the alpha 2-adrenoceptor agonist, UK-14,304.

1. The influence of the alpha 2-adrenoceptor agonist, UK-14,304, on non-adrenergic non-cholinergic (NANC) relaxation induced by electrical field stimulation was investigated in longitudinal muscle strips of the gastric fundus of reserpinized rats. 2. In tissues where tone was raised by 3 x 10(-7) M prostaglandin F2 alpha (PGF2 alpha), the inhibitory effect of 10(-6) M UK-14,304, on the NANC relaxations induced by short train stimulation (40 V, 1 ms, 20 s) was inversely related to the stimulus frequency (1-4-16 Hz). UK-14,304 (10(-6) M) did not influence relaxations induced by administration of exogenous nitric oxide (NO, 2 x 10(-6) M-10(-4) M). The inhibitory effect of UK-14,304 on the electrically induced relaxations was antagonized by 10(-6) M rauwolscine but not by 10(-6) M prazosin. 3. UK-14,304 (10(-6) M) also reduced the amplitude of the sustained NANC relaxation, induced by electrical field stimulation (40 V, 1 ms, 4 Hz) for 5 min. The effect of UK-14,304 was also antagonized by 10(-6) M rauwolscine but not by 10(-6) M prazosin. UK-14,304 (10(-6) M) did not reduce the relaxation induced by 3 x 10(-9) M vasoactive intestinal polypeptide (VIP). 4. These results suggest that the release of the inhibitory NANC neurotransmitter during short train stimulation, thought to be NO, and during sustained stimulation, thought to be VIP, is inhibited by stimulation of presynaptic alpha 2-adrenoceptors in the rat gastric fundus.

Adrenergic alpha-Agonists↗

PubMed1991

Influence of thiorphan and phosphoramidon on the relaxant effect of vasoactive intestinal polypeptide and non-adrenergic non-cholinergic neurone stimulation in the rat gastric fundus.

Relaxations were induced in longitudinal muscle strips of the rat gastric fundus by exogenous administration of vasoactive intestinal polypeptide (VIP) and by transmural stimulation in the presence of atropine. These responses were not influenced by two neutral endopeptidase inhibitors, thiorphan (3 X 10(-5) M) and phosphoramidon (10(-5) M). This suggests that neutral endopeptidase is not involved in the breakdown of exogenous VIP and non-adrenergic non-cholinergic inhibitory transmitters of the rat gastric fundus.

Animals↗

PubMed1991

Hemodynamic basis for the depressor activity of zaprinast, a selective cyclic GMP phosphodiesterase inhibitor.

The present investigation was undertaken to define the hemodynamic mechanisms by which the selective cyclic GMP phosphodiesterase inhibitor zaprinast (M&B 22,948; 2-o-propoxy-phenyl-8-azapurin-6-one) lowers mean arterial pressure (MAP). Anesthetized rats were instrumented with electromagnetic or pulsed-Doppler flow probes to measure cardiac output or regional blood flow, respectively, and catheters to record MAP, left ventricular pressure and administer drugs. Zaprinast (0.33-2.0 mg.min-1.kg-1) produced dose-dependent decreases in MAP (maximum = -39 +/- 6 mm Hg) and total peripheral resistance (maximum = -45 +/- 5%) when infused i.v. The greatest reductions in regional vascular resistance were observed in the mesenteric bed, with smaller decreases in the hindquarters and renal beds. Cardiac output increased (maximum = 22 +/- 7%) during the infusion of zaprinast; however, heart rate was only minimally affected. These increases in cardiac output were still evident in animals pretreated with beta adrenergic and muscarinic receptor antagonists. At the lowest dose, zaprinast tended to increase maximal first derivative of left ventricular pressure, whereas, at higher doses maximal first derivative of left ventricular pressure was depressed or unchanged. Additional studies were performed to examine the effect of the cyclic GMP phosphodiesterase inhibitor on the pressor and vasoconstrictor activity of phenylephrine and angiotensin II. The increases in MAP and total peripheral resistance produced by these agents were attenuated markedly during continuous infusion of zaprinast (1 mg.min-1.kg-1). These data suggest that zaprinast lowers MAP by decreasing peripheral vascular resistance and by antagonizing the actions of endogenous neurohumoral vasoconstrictor systems.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1991

Reversal of low dose angiotension hypertension by angiotensin receptor antagonists.

During acute angiotension II (Ang II) infusion (200 ng/kg/min i.v.) into anesthetized rats, mean arterial pressure rose from 124 +/- 1 to 154 +/- 2 mm Hg. The peptidic Ang II antagonist saralasin lowered arterial pressure in a dose-dependent manner. The maximal decrease in pressure was similar to that observed after the Ang II infusion was discontinued. The nonpeptide Ang II antagonist, 4'-[( 2-butyl-4-chloro-5-(hydroxymethyl)-1H-imidazole-1-yl] methyl) [1,1'-biphenyl] -2-carboxylic acid (SC-48742), lowered acutely elevated arterial pressure to a level similar to that on discontinuation of the angiotensin infusion. Chronic (8 days) infusion of Ang II (20 ng/kg/min i.v.) increased mean arterial pressure from 116 +/- 3 to 164 +/- 7 mm Hg, which then decreased to 121 +/- 6 mm Hg on termination of the infusion. Saralasin (10 micrograms/kg/min, a maximally effective dose during acute angiotensin infusion) decreased mean arterial pressure from 168 +/- 7 to 141 +/- 3 mm Hg, a pressure significantly higher (p less than 0.05) than the pressure observed after the angiotensin infusion was discontinued. SC-48742 decreased mean arterial pressure from 167 +/- 7 to 127 +/- 3 mm Hg, a pressure not statistically different from the minimum pressure observed after the angiotensin infusion was terminated. The mechanism of blood pressure elevation during acute high dose or chronic low dose Ang II infusion is different, the latter having a significant neural component as measured by the response to trimethaphan. The peptidic antagonist saralasin was fully effective in lowering acute angiotensin hypertension but only partially effective during chronic hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of Variance↗

PubMed1990

Structure-activity relationships for the carboxy-terminus truncated analogues of angiotension II, a new class of angiotensin II antagonists.

A series of analogues of the recently reported angiotensin II (AII) antagonist [Sar1]AII-(1-7)-amide or des-Phe8[Sar1]AII (3) have been prepared by solid-phase synthesis and purified by reverse-phase liquid chromatography. The agonist and antagonist properties of these carboxy-truncated analogues of AII were determined in the isolated rabbit aorta assay. In the analogues tested, replacement of aspartic acid in position 1 by sarcosine was found necessary to produce significant antagonist activity. At position 7 of the des-Phe8 analogues, prolinamide could be replaced by proline without significant change in the biological activity. However, substitution of 7-prolinamide by either glycinamide or sarcosinamide provided inactive peptides. Methylation of the 4-tyrosine in [Sar1]AII-(1-7)-NH2 preserved the antagonist potency in isolated rabbit aorta. Deletion of the proline at position 7 resulted in inactive hexapeptides, both in the Asp1 and Sar1 series. However synthesis of the N,N-dimethyl amide at the N-terminus afforded hexapeptide [Sar1]AII-(1-6)-N(CH3)2 (10) with a pA2 value of 7.05. All the antagonistic peptides synthesized were fully reversible, competitive antagonists in vitro. These findings indicate that the structural requirements for receptor blockade by these C-truncated analogues are quite stringent with respect to the nature of the amino acid at positions 1 and 6/7. The analogues 2, 3, 7, 10, 11 (saralasin), and 12 (sarmesin) were tested in vivo in the anesthetized rat and were found to inhibit the AII pressor response. In addition, 3 inhibited angiotensin II stimulated aldosterone release from isolated rat adrenal zona glomerulosa cells and had no agonist activity by itself at the doses tested. Interestingly, analogue 3, when injected intracerebroventricularly in conscious rats, failed to antagonize the dipsogenic response to an angiotensin II icv injection and this reflects some heterogeneity in the AII receptor population. Peptide 3 is the first example of an antagonist that discriminates between peripheral and brain receptor subtypes.

Angiotensin II↗

PubMed1990

Interaction of ANP and bradykinin during endopeptidase 24.11 inhibition: renal effects.

Experiments were performed on anesthetized rats to determine whether inhibition of endopeptidase 24.11 (EP) potentiates the biological activity of atrial natriuretic peptide, ANP-(99-126), and to examine the mechanisms that underlie this effect. Thiorphan (30 mg/kg iv), an inhibitor of EP, produced a modest increase in urinary sodium excretion when administered alone but did not affect urine flow, mean arterial pressure (MAP), or the endogenous level of plasma ANP. The infusion of ANP-(99-126) alone (67 ng.kg-1.min-1 iv) produced a modest natriuresis and decrease in MAP while increasing plasma ANP levels fivefold. When thiorphan (30 mg/kg iv) was administered during the ANP infusion, urine flow and urinary sodium excretion increased markedly but no further decrease in MAP or increase in plasma ANP levels was observed. This potentiation of the renal actions of ANP was not mediated by inhibition of angiotensin-converting enzyme, an increase in glomerular filtration rate, or an increase in renal blood flow but was completely abolished by a specific antagonist of the bradykinin receptor [( DArg0, Hyp3, Thi5, DPhe7, Thi8]bradykinin, 30 micrograms.kg-1.min-1 iv). These data suggest that inhibitors of EP can potentiate the renal activity of ANP by a mechanism which is independent of altered ANP catabolism and which may involve the accumulation of bradykinin, another substrate for EP, within the kidney.

Animals↗

PubMed1990

Effect of endopeptidase 24.11 inhibition in conscious cardiomyopathic hamsters.

An elevated plasma concentration of atrial natriuretic peptide (ANP) is characteristic of congestive heart failure (CHF) in both humans and animals. One strategy for facilitating the biological actions of this circulating hormone is to inhibit its metabolism. Neutral endopeptidase 24.11, an enzyme known to degrade ANP, has been implicated in the metabolic clearance of this hormone. Inhibition of endopeptidase 24.11 may produce increases in the local concentrations of ANP in organs rich in the enzyme, such as the kidney, thereby enhancing local actions, e.g. natriuresis. Exogenous administration of ANP to CHF patients produces limited natriuresis, perhaps because of the associated fall in arterial pressure. This approach of blocking endopeptidase 24.11 activity in CHF could offset the general effects of exogenous administration of ANP and result in enhanced natriuresis. We therefore undertook studies to determine if thiorphan, an endopeptidase 24.11 inhibitor, would increase circulating ANP levels and enhance natriuresis in conscious cardiomyopathic hamsters with CHF. Cardiomyopathic hamsters had significantly lower (P less than .05) basal mean arterial pressures in comparison to normal hamsters (90 +/- 2 vs. 135 +/- 3 mm Hg). Treatment with thiorphan (10 mg/kg i.v. bolus followed by 10 mg/kg/hr i.v. infusion) did not change arterial pressure in either group and produced a 3-fold increase in urinary sodium excretion in the cardiomyopathic group but not in the normal hamsters. This natriuretic response in the cardiomyopathic hamsters was associated with a doubling of the plasma concentration of ANP. These results indicate that inhibition of endopeptidase 24.11 increases natriuresis and circulating ANP concentrations in this model of CHF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Thiorphan, an inhibitor of endopeptidase 24.11, potentiates the natriuretic activity of atrial natriuretic peptide.

To evaluate the role of endopeptidase 24.11 in metabolism of atrial natriuretic peptide (ANP) in vivo, we examined the effect of thiorphan, an inhibitor of this enzyme, on plasma ANP concentrations and the cardiovascular and renal actions of ANP(99-126). Thiorphan alone produced a modest increase in urinary sodium excretion in anesthetized rats; however, urine flow, arterial pressure, and basal plasma ANP concentrations were unchanged. When administered during an infusion of ANP(99-126) (330 ng/kg/min i.v.), thiorphan increased the plasma concentration of ANP and enhanced the diuretic and natriuretic activity of this hormone. The effects on urine flow and urinary sodium excretion were most pronounced immediately after the inhibitor was administered and later diminished in magnitude. Thiorphan did not alter the depressor activity of exogenous ANP(99-126). These data suggest that endopeptidase 24.11 participates in metabolism of ANP(99-126) and that thiorphan potentiates the renal actions of this hormone by inhibiting its degradation.

Animals↗

PubMed1986

Evaluation of laser-Doppler flowmetry as a measure of tissue blood flow.

In this study the technique of laser-Doppler flowmetry was evaluated for the measurement of tissue blood flow by comparing laser-Doppler flow (LDF) signal in the renal cortex, gracilis muscle, and cremaster muscle of anesthetized rats to whole-organ blood flow measured with an electromagnetic flowmeter or radioactive microspheres. In vitro, LDF signal was closely correlated (r = 0.99) to changes in erythrocyte velocity generated with a rotating wheel. Although individual LDF readings varied in situ, mean LDF signal calculated from multiple readings on the tissue surface were significantly correlated (r = 0.74-0.95) with tissue blood flows measured at various perfusion pressures. However, significant differences in the slope of the LDF signal vs. blood flow relationship were observed in different tissues and with different methods of measurement in the same tissue. This study indicates that mean laser-Doppler flow signal provides a good estimate of tissue blood flow, provided a sufficient number of points is scanned. However, there appears to be no universal calibration factor for the method.

Animals↗