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Biomedical subjects

M J Peach

Publications and source records attributed to M J Peach.

At least 145 records · Page 8Linked to original sources
PubMed1978

Blood pressure support during general anesthesia in a renin-dependent state in the rat.

Previous work had shown that halothane and enflurane at 1 MAC and ketamine, 125 mg/kg, did not increase plasma renin activity (PRA) in the normal sodium-replete rat. To investigate the renin-angiotensin system with increased PRA, 25 rats were fed a low-sodium diet for five to seven days and divided into four groups: awake; halothane, 1.26 vol per cent; enflurane, 1.75 vol per cent; ketamine, 125 mg/kg, intramuscularly. The protocol consisted of a two-hour awake period, then an hour of stable anesthesia, followed by 30 min infusion of saralasin, an angiotensin II competitive inhibitor. An additional 18 rats had PRA measured by radioimmunoassay before and after an hour of stable anesthesia. Stable anesthesia decreased mean arterial pressure from 122 +/- 2 to 69 +/- 4 torr for the halothane group, 70 +/- 3 torr for the enflurane group, and 103 +/- 7 torr for the ketamine group. When saralasin was infused for 30 min, blood pressure decreased to 100 +/- 3 torr for the awake group, 40 +/- 1 torr for the halothane group, 44 +/- 2 torr for the enflurane group, and 73 +/- 3 torr for the ketamine group. PRA increased from 4.3 +/- 0.5 ng/ml/hr for sodium-replete rats to 12.9 +/- 1.7 ng/ml/hr for sodium-depleted rats. After an hour of stable anesthesia, PRA increased in all the anesthetized groups. The authors conclude that the anesthetic agents studied increase renin release in the sodium-depleted rat. The initial renin level may be important in determining whether changes in renin release occur with anesthetic agents.

Anesthetics↗
PubMed1978

Sodium cyanide antagonism of the vasodilator action of sodium nitroprusside in theisolated rabbit aortic strip.

Resistance to sodium nitroprusside (SNP) is uncommon, but its occurrence has led to massive overdoses of SNP and sometimes death. To examine the mechanism responsible for resistance, aortic smooth muscle strips were prepared and dose-response curves for norepinephrine (NE) obtained. SNP alone caused a shift of the dose-response curve for NE to the right. However, this shift was less when the strips were exposed to both SNP and sodium cyanide (CN-). When CN- alone was added to the aortic strips, the response to NE was unchanged. In a further group of aortic muscle strips first contracted with NE and then relaxed with SNP, the addition of CN- caused the muscles to contract again. It is concluded that CN- antagonizes the action of SNP in vitro, and that this antagonism is specific for SNP.

Animals↗
PubMed1978

Activation of the alternative pathway of complement by grain. I. C3PA conversion and quantification of complement consumption by rye.

Ground whole rye and airborne rye dust of comparable size distribution were tested for their ability to activate the complement cascade via the alternative pathway. Precipitin-negative pooled normal human serum was incubated with increasing amounts of the two rye dusts. Electrophoresis of the resultant supernatant fluids demonstrated the conversion of the proactivator of the third component of complement to the gamma-migrating activator of the third component. This activation was completely prevented by pre-treating the serum with the chelator EDTA, while pre-treatment with EGTA allowed suboptimal arc conversion, strongly implying that complement was activated via the alternative pathway. Quantification of the supernanant fluids showed dose-dependent complement consumption as defined by both CH100 immunodiffusion and CH50 tube haemolytic techniques. Airborne rye dust showed a greater quantitative potential than ground whole rye for activating the alternative pathway. These results indicate the possibility of the direct action of airborne organic dusts on the induction of inflammatory sequelae in the lungs of both sensitized and unsensitized individuals.

Air Pollutants↗
PubMed1978

Activity of (des-Aspartyl1)-angiotensin II and angiotensin II in man. Differences in blood pressure and adrenocortical response during normal and low sodium intake.

This study was designed to compare the effect of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-A II) and angiotensin II (A II) on blood pressure and aldosterone production in man under conditions of normal and low sodium (Na) intake. Seven normal male subjects in balance on constant normal Na intake (U(Na) V 160.3+/-5.0 meq/24 h) for 5 days received A II and [des-Asp]-A II infusions on two consecutive days; 1 mo later they were restudied after 5 days of low Na intake (U(Na) V 10.5+/-1.6 meq/24 h). Each dose was infused for 30 min, sequentially. During normal Na intake, [des-Asp]-A II from 2 to 18 pmol/kg per min increased mean blood pressure from 85.2+/-3 to 95.3+/-5 mm Hg and plasma aldosterone concentration from 5.2+/-1.1 to 14.3+/-1.9 ng/100 ml. During low Na intake, the same dose of [des-Asp]-A II increased mean blood pressure from 83.7+/-3 to 86.7+/-3 mm Hg and plasma aldosterone concentration from 34.4+/-6.0 to 51.0+/-8.2 ng/100 ml. In contrast, A II from 2 to 6 pmol/kg per min during normal Na intake increased mean blood pressure from 83.3+/-4 to 102.3+/-4 mm Hg and plasma aldosterone concentration from 7.0+/-2.2 to 26.8+/-2.0 ng/100 ml; during low Na intake, A II increased mean blood pressure from 83.0+/-3 to 96.0+/-4 mm Hg and plasma aldosterone concentration from 42.0+/-9.7 to 102.2+/-15.4 ng/100 ml. A II and [des-Asp]-A II were equally effective in suppressing renin release. Plasma cortisol and Na and K concentration did not change. The effects of two doses (2 and 6 pmol/kg per min) of each peptide on blood pressure and aldosterone production were evaluated. During normal Na intake, [des-Asp]-A II had 11-36% of the pressor activity and 15-30% of the steroidogenic activity of A II. Na deprivation attenuated the pressor response and sensitized the adrenal cortex to both peptides, but the increase in steroidogenesis was greater with [des-Asp]-A II than with A II. The dose-response curves for [des-Asp]-A II with respect to blood pressure and aldosterone production were not parallel, and although no maximum was established for A II, [des-Asp]-A II was less efficacious.In summary, (a) [des-Asp]-A II has biologic activity in man, (b) [des-Asp]-A II is less efficacious than A II in stimulating aldosterone production, (c) Na deprivation sensitizes the adrenal cortex more markedly to [des-Asp]-A II than A II, and (d) dose-response curves for the two peptides differ, suggesting the possibility that they act at different receptor sites in vascular smooth muscle and the adrenal cortex.

Adrenal Glands↗
PubMed1978

The immediate pressor effect of saralasin in man.

An immediate pressor response to [Sar1-Ala8]-angiotensin II (saralasin) is described in all of 16 hypertensive subjects. Blood pressure rose within 1-3 min, peaked at 4-6 min, then returned toward baseline. Plasma norepinephrine and dopamine beta-hydroxylase activity were unchanged by saralasin, indicating that the pressor response is not mediated by saralasin-induced catecholamine release. Ten normal renin hypertensives had diastolic pressor responses of 19.4 +/- 3.3 mm Hg. After 5 weeks of diuretic therapy, the diastolic pressor responses to saralasin were decreased to 4.9 +/- 2.4 mm Hg. Six low renin hypertensives had diastolic pressor responses of 26.2 +/- 6.2 mm Hg, but 5 weeks of diuretic therapy did not decrease these pressor responses significantly. In two normal and two low renin hypertensives, the diastolic blood pressure rose to levels greater than 150 mm Hg. The amplitudes of the immediate pressor responses were inversely correlated with the base-line plasma renin activities, r = -0.46. The data support the concept that the agonist activity of saralasin occurs at the angiotensin II vascular receptor level with clinical expression mediated by sodium and/or volume changes.

Angiotensin II↗
PubMed1977

Peptide antagonists of angiotensin-induced adrenal catecholamine release.

The effect of analogs of angiotensin (modified with an Ile-substituted for Phe) was studied in the isolated, retrogradely perfused adrenal of the cat. Continuous differential analysis of norepinephrine and epinephrine output was quantified with an automated trihydroxyindole procedure. [Ile8]-angiotensin I and [Ile7]-angiotensin III exhibited negligible secretory activity, in contrast to the stimulatory effects of [Ile8]-angiotensin II (10-20% activity relative to angiotensin II). [Ile8]-angiotensin I blocked angiotensin II-induced catecholamine secretion and a pA2 value of 8.50 was obtained. [Ile7]-angiotensin III was an especially potent antagonist of angiotensin II and a pA2 value of 10.4 was calculated for this heptapeptide analog. The pA2 value for [Ile8]-angiotensin II, a partial agonist in the adrenal medulla was 9.33. These three analogs were equally effective against secretion induced by the corresponding unsubstituted homologs (Ang I and Ang III). These data suggest that all these angiotensin peptides interact with a common receptor. [Ile8]-angiotensin I and [Ile7]-angiotensin III had no effect on adrenal medullary responses induced by KCl, nicotine and bradykinin. These structural analogs of angiotensin are pure competitive antagonists of angiotensin in the cat adrenal chromaffin cell.

Adrenal Glands↗
PubMed1977

Demonstration of different contractile mechanisms for angiotensin II and des-Asp1-angiotensin II in rabbit aortic strips.

Evidence of selective inhibition, differences in dose-response relationships, and cross-tachyphylaxis studies suggest that separate receptors and/or mechanisms may be involved in responses to angiotensin (Ang), [Sar1]Ang II, and Ang III (= des-Asp1-Ang II). The extracellular Ca2+ requirement for contractile responses induced by angiotensin peptides and norepinephrine was determined in rabbit aortic strips. Responses to K+ and [Sar1]Ang II were attenuated markedly by treatment with SKF-525A, verapamil, or Ca2+-free buffer. The response to Ang II was not impaired by verapamil, was blocked partially by SKF-525A, and was reduced markedly in Ca2+-free medium. Norepinephrine- and Ang III-induced contractions were not dependent on extracellular Ca2+. K+, Ang II, and [Sar1]Ang II required extracellular Ca2+ to induce contraction of the rabbit aorta. The data indicate that Ang III may have a mechanism of action that differs from that of [Sar1]Ang II and Ang II.

Angiotensin II↗
PubMed1977

Pressor and stereoidogenic actions of [des-Asp1]angiotensin I dependency on conversion to angiotensin III.

In the conscious rat, angiotensin III, [des-Asp1]angiotensin II, stimulates aldosterone biosynthesis and exhibits 30-50% of the pressor potency of angiotensin II. A potential precursor of the biologically active heptapeptide is [des-Asp1]angiotensin I, the C-terminal nonapeptide of angiotensin I. The in vivo pressor and the in vivo and in vitro steroidogenic actions of [des-Asp1]angiotensin I were investigated in the presence and absence of an inhibitor of converting enzyme. The pressor responses to [des-Asp1]angiotensin I and [des-Asp1]angiotensin II were similar and showed comparable changes in responsiveness when the rats were maintained on diets with different sodium content. The pressor activity of [des-Asp1]angiotensin I was attenuated progressively by pretreatment with increasing doses of converting enzyme inhibitor and was totally abolished in five of seven rats at an inhibitor dose of 1,200 microng/kg. In isolated zona glomerulosa cells from rats on normal sodium diets, angiotensin I and [des-Asp1]angiotensin I had only weak steroidogenic effects relative to angiotensin III. The administration of [des-Asp1]angiotensin I, 1 nmol/kg, subcutaneously to six rats on normal sodium diets resulted in a rise in the 6-hour urinary aldosterone excretion from 46.5 +/- 6.6 to 99.5 +/- 11.8 ng (P less than 0.01). Treatment with converting enzyme inhibitor (2 mg/kg) prevented this steroidogenic response to [des-Asp1]angiotensin I. These in vivo studies in the conscious rat show that the administration of [des-Asp1]angiotensin I results in increases in both blood pressure and urinary aldosterone excretion which are dependent on the hydrolysis of the nonapeptide by converting enzymes to angiotensin III. If [des-Asp1]angiotensin I is formed in this species, then it will be an immediate precursor of angiotensin III.

Adrenal Cortex↗
PubMed1976

Des-Asp1-angiotensin I: a metabolite of angiotensin I in the perfused feline adrenal.

The administration of radioactive angiotensin I to the retrogradely perfused feline adrenal gland caused a brisk discharge of catecholamines. Recovery of the labelled decapeptide and metabolites in the adrenal effluent fluid was complete in 5 min. Radioimmunoassay of this perfusate revealed that most of the peptide remained as angiotensin I, but chromatographic and electrophoretic evaluation indicated that greater than 68% of the peptide had been metabolized to des-asp1 -angiotensin I. The absence of des-asp1 -angiotensin II, angiotensin II or his-3H-leu in adrenal effluent fluid suggested minimal dipeptidyl carboxypeptidase activity in this preparation. In addition, the profile of angiotensin I metabolites from the perfused adrenal was not altered by treatment with a converting enzyme inhibitor B. jararaca nonapeptide. The des-asp1-angiotensin I peptide was a very weak secretagogue in the adrenal medulla. If metabolism of the decapeptide to the nonapeptide occurs in the medulla, this may represent a pathway to limit the secretory action of angiotensin I. These results suggest a high degree of adrenal aminopeptidase activity which may be primarily localized in the adrenal cortex.

Adrenal Glands↗
PubMed1976

Synthesis of angiotensin II antagonists containing N- and O-methylated and other amino acid residues.

[1-N-Methylisoasparagine,8-isoleucine]- (I), [1-sarcosine,4-N-methyltyrosine,8-isoleucine]- (II), [1-sarcosine,5-N-methylisoleucine,8-isoleucine]- (III), [1-sarcosine,8-N-methylisoleucine]- (IV), [1-sarcosine8k-N-methylisoleucine,8-N-methylisoleucine]- (V), [1-sarcosine,8-O-methylthreonine]- (VI), [1-sarcosine,8-methionine]- (VII), and [1-sarcosine,8-serine]angiotensin II (VIII), synthesized by Merrifield's solid-phase procedure, possess respectively 0.8, 0.3, 0.5, 1.0, 0.0, 0.5, 3.7, and 0.7% pressor activity of angiotensin II (vagotomized, ganglion-blocked rats). They caused an initial rise in blood pressure (30 min of infusion, 250 ng/kg/min in vagotomized, ganglion-blocked rats) of 16.57, 9.80, 22.80, 32.00, 7.00, 15.06, 32.50, and 11.42 mmHg and showed secretory activity (isolated cat adrenal medulla) of 1.0, 0.1, 0.01, 0.1, less than 0.01, 0.1, less than 0.01, and 0.05% of angiotensin II. On isolated organs pA2 values (rabbit aortic strips) of 8.74, 7.44, 7.64, 7.85, 7.89, 8.76, 8.63, and 8.08, and pA2 values (cat adrenal medulla of 8.16, 9.16, 9.31, 8.00, 8.00, 7.00, 9.16, and 9.33 were obtained. Dose ratios (ratio of ED20 of angiotensin II during infusion of the antagonist and before infusion of the antagonist) in vagotomized, ganglion-blocked rats, infused at 250 ng/kg/min, were 33.43, 2.14, 3.26, 2.99, 0.62, 62.52, incalculable, and 11.15, respectively. The results obtained suggest that (a) analogs I and VI are potent antagonists of the pressor response of angiotensin II in normal rat, VI being the most potent antagonist thus far synthesized; (b) replacement of position 4 (Tyr) with MeTyr or position 5 and/or 8 (Ile) with Melle in [1-sarcosine,8-isoleucine]angiotensin II reduced the antagonist activity of this peptide (rabbit aortic strips and rats), indicating that steric hindrance imposed due to N-methylation in positions 4, 5, or 8 was not favorable in eliminating the initial pressor activity or prolonging the duration of action of [Sar1, Ile8]angiotensin II without reducing its antagonistic properties; (c) except II, none of the analogs showed any enhanced duration of action, suggesting that N-methylation in positions 5 or 8 did not afford protection against proteolytic enzymes; and (d) perfusion studies in cat adrenals indicated that all of these analogs are only very weak secretagogues. With the exception of [Sar1,Thr(ObetaMe)8]angiotensin II, which gave lower antagonistic properties, all other analogs had either similar antagonistic properties or were better antagonists in adrenal medulla than in smooth muscle.

Adrenal Glands↗