Biomedical subjects

E J Sybertz

Publications and source records attributed to E J Sybertz.

At least 55 records · Page 3Linked to original sources

PubMed1988

Phorbol 12,13-dibutyrate, an activator of protein kinase C, stimulates both contraction and Ca2+ fluxes in dog saphenous vein.

The vascular effects of phorbol 12,13-dibutyrate (PDBu) were studied in the dog saphenous vein. PDBu (1 microM) caused contraction (0.58 +/- 0.22 g/mg wet wt.) and Ca uptake (74.2 +/- 41.2 mumol/kg wet wt.) which were unaffected by 10 microM phentolamine (N = 6). The PDBu-induced contraction was greatly (60-80%) inhibited in Ca2+-free solution. 45Ca efflux measurements performed in Ca2+-free solution showed that PDBu did not cause Ca release from intracellular storage sites. The contractile response to PDBu (1 nM-1 microM) was significantly correlated with the magnitude of Ca uptake; contraction and the rise in tissue Ca2+ also had a similar time course. Correlation between the two measures persisted when the responses to PDBu were augmented by co-administration with 20 mM KCl. However, no synergism occurred between the two agonists. Both the contraction and Ca uptake responses to PDBu were reduced by nifedipine and verapamil, each at 1 microM. In the Triton X-100 skinned saphenous vein, where the voltage-dependent Ca channel is not functional, 10 microM PDBu did not cause contractions in the presence of 0.1 microM Ca2+. Thus, contraction of the intact saphenous vein by PDBu characteristically exhibits great Ca dependence and PDBu seems to activate the voltage-dependent Ca channel, presumably through stimulation of protein kinase C; the ensuing Ca entry is primarily responsible for contraction. However, the mechanism responsible for the PDBu-induced contractions that are resistant to Ca2+-free PSS or Ca entry blockers remains to be defined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1988

Synthesis and pharmacological activity of angiotensin converting enzyme inhibitors: N-(mercaptoacyl)-4-substituted-(S)-prolines.

The synthesis of a series of N-(mercaptoacyl)-4-substituted-(S)-prolines (2 and 3) is described. These compounds were evaluated in vitro for inhibition of angiotensin-converting enzyme (ACE), and selected compounds were evaluated in vivo for ACE inhibition. The most potent compounds in vitro are 108, 109, 111, 114, and 116, having relative potencies of 1.0, 1.0, 1.3, 1.1, and 2.6 as compared to the potency of captopril. The most potent compounds in vivo intravenously are 108, 111, 114, 116, 117, and 97.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1988

Comparative effects of vinpocetine and 8-Br-cyclic GMP on the contraction and 45Ca-fluxes in the rabbit aorta.

Vinpocetine is a highly specific inhibitor of calmodulin-dependent phosphodiesterase (CaM-PDE) with an IC50 of 19 microM and produces a significant accumulation of cyclic GMP but not cyclic AMP in rabbit aorta. In isolated rabbit aortic strips, vinpocetine (0.01 and 0.1 mM) inhibited the contraction and 45Ca uptake due to both phenylephrine (1 microM) and KCl (40 mM), whereas 8-Br-cyclic GMP (0.1-1mM) selectively impaired phenylephrine-induced responses. Furthermore, the KCl-stimulated 45Ca efflux in normal Ca2+ buffer, which reflects elevated cytosolic Ca2+, was greatly diminished by vinpocetine but not by 8-Br-cyclic GMP. However, phenylephrine-induced 45Ca efflux and contraction in Ca2+-free buffer, which reflect Ca2+ release from intracellular sites, were similarly inhibited by both vinpocetine and 8-Br-cyclic GMP. The results suggest that vinpocetine may effect vasodilatation through blockade of the slow channel and selective inhibition of CaM-PDE in the vascular smooth muscle.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1988

Effects of the antihypertensive dilevalol on aortic compliance in anesthetized dogs.

The present study examined the actions of dilevalol, an antihypertensive beta-adrenoceptor blocker with arterial vasodilator actions, on aortic compliance (AC) in anesthetized dogs. AC was measured by sonomicrometric determination of the ratio of aortic systolic-diastolic diameters (mm) and arterial pulse pressure (mm Hg). One AC unit (ACU) equals 10(-3) mm/mm Hg. Dilevalol (0.032, 0.1, and 3.2 mg/kg intravenously, i.v.) significantly (p less than .05) increased AC by 1.4 +/- 0.3, 3.7 +/- 1.4, and 4.5 +/- 1.2 ACU from basal values of 4.7 +/- 0.4-5.6 +/- 0.4 ACU while reducing blood pressure by 20 +/- 2, 31 +/- 9, and 41 +/- 10 mm Hg, respectively (p less than 0.05). Increases in AC were not the passive result of altered blood pressure. Proximal mechanical aortic occlusion dropped systolic blood pressure as much as 70 mm Hg without altering AC. Hydralazine also (0.3 and 1.0 mg/kg i.v.) lowered blood pressure significantly (p less than 0.05) by 14 +/- 3 and 40 +/- 4 mm Hg but increased AC only at 1.0 mg/kg (+ 1.6 +/- 0.4 ACU, p less than 0.05). Phenylephrine (1-30 micrograms/kg i.v.) significantly raised blood pressure 25 +/- 3-95 +/- 8 mm Hg but decreased AC significantly by 1.2 +/- 0.3-2.4 +/- 0.3 ACU. Isoproterenol (ISO) (0.01-1.0 micrograms/kg) produced effects on AC similar to those of dilevalol. Propranolol pretreatment attenuated dilevalol and ISO-induced increases in AC. Propranolol (0.32 and 1.0 mg/kg) did not significantly change AC.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

PubMed1987

The responses of atrial natriuretic factor concentrations to acute volume changes in conscious rats.

A rapid and sensitive radioimmunoassay has been developed for measurements of atrial natriuretic factor (ANF) in rat plasma. The antiserum, raised to rat ANF (99-126), cross-reacts with rat ANF (103-123), ANF (103-125), ANF (103-126) but not with smaller fragments, human ANF (99-126), angiotensin II, bradykinin or vasopressin. The plasma ANF concentration is 181 +/- 24 pg/ml (N = 24) in the unstressed conscious rats (Charles River CD, male). The ANF immunoreactivity in the plasma extracts was verified by HPLC analysis, which displayed one major immunoreactive peak of ANF corresponding to rat ANF (99-126) and some smaller fragments. Intravenous injection of saline elevated circulating ANF, whereas acute volume depletion by hemorrhage, water deprivation and furosemide diuresis greatly lowered plasma ANF. The prompt response of plasma ANF levels to acute changes in volume status is consistent with the proposed role of ANF as a volume-regulatory hormone.

Animals↗

PubMed1987

Nitroprusside, but not ANF inhibits venoconstriction in an in situ rat model.

Potential venodilator actions of nitroprusside (10 and 50 micrograms/min) and ANF (23 amino acid rat sequence, 10 and 30 micrograms/min) were assessed in rats subjected to cardiopulmonary bypass. Norepinephrine (NE, 10 micrograms) caused arterial pressor, i.e. increased perfusion pressure and venoconstrictor, i.e. increased venous flow, effects. ANF infusion failed to alter NE-induced pressor and venoconstrictor effects while nitroprusside significantly inhibited NE responses. Thus nitroprusside but not ANF, shows venodilator properties in this in situ rat model.

Animals↗

PubMed1987

Pharmacologic, metabolic, and toxicologic profile of spirapril (SCH 33844), a new angiotensin converting inhibitor.

Spirapril (SCH 33844; 7-N-[1(S)-ethoxycarbonyl-3-phenylpropyl]-(S)-alanyl-1,4-dithia- 7-azaspiro[4,4]-nonane-8(S)-carboxylic acid) is a new angiotensin-converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of hip-his-leu by rabbit lung ACE in a potent (Ki = 0.74 nM), selective, and noncompetitive fashion. SCH 33844 (0.03-1 mg/kg p.o.) produced dose-related inhibition of angiotensin I (AI) pressor responses in conscious rats with a duration of 24 h at the higher dose. SCH 33844 (0.3-30 mg/kg p.o.) reduced blood pressure in a dose-related manner in conscious SHR with a 24-h duration. Antihypertensive activity was enhanced in the presence of hydrochlorothiazide. The drug (1-10 mg/kg p.o.) also lowered blood pressure in conscious hydrochlorothiazide-treated normotensive dogs. In anesthetized dogs, SCH 33844 (1 mg/kg i.v.) reduced blood pressure and total peripheral vascular resistance and slightly increased cardiac output and stroke volume. These results suggest that peripheral vasodilation is the primary mechanism of the antihypertensive action. The metabolic profile of SCH 33844 was evaluated in dogs and rats. The compound was absorbed in a dose-proportional manner and excreted primarily as the diacid form. In contrast to captopril and enalapril, most of the drug (67%) was excreted into the feces following i.v. dosing. Chronic toxicological evaluation in dogs and rats demonstrated that the drug was relatively devoid of toxicity at oral doses as high as 400 and 450 mg/kg/day, respectively. Slight decreases in heart weight (rats) and increases in granularity of the juxtaglomerular apparatus were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Effects of the antihypertensive dilevalol on large artery compliance in anesthetized dogs.

The present study examined the actions of dilevalol, an antihypertensive beta-adrenoceptor blocker with arterial vasodilator actions, upon aortic compliance (AC) in anesthetized dogs. AC was determined via sonomicrometric determination of the ratio of aortic systolic-diastolic diameters (mm) and arterial pulse pressure (mm Hg). One AC unit (ACU) equals 10(-3) mm/mm Hg. Dilevalol (0.032, 0.1, and 3.2 mg/kg i.v.) significantly (p less than 0.05) increased AC by 1.4 +/- 0.3, 3.7 +/- 1.4, and 4.5 +/- 1.2 ACU, respectively, from basal values of 4.7 +/- 0.4-5.6 +/- 0.4 ACU, while reducing blood pressure by 20 +/- 2, 31 +/- 9, and 41 +/- 10 mm Hg, respectively (p less than 0.05). Increases in AC were not the passive result of altered blood pressure. Proximal mechanical aortic occlusion dropped systolic blood pressure as much as 70 mm Hg without altering AC. Propranolol (0.32 and 1.0 mg/kg) did not significantly change AC, but propranolol pretreatment attentuated dilevalol-induced increases in AC. Pindolol (0.1-1.0 mg/kg i.v.) lowered blood pressure 17 +/- 3 (p less than 0.05) to 34 +/- 7 mm Hg (p less than 0.05), while significantly increasing AC by 1.2 +/- .2 to 2.7 +/- .7 ACU. The data show that dilevalol, unlike propranolol, increases AC substantially at antihypertensive doses. The inhibition of dilevalol-induced AC increases by propranolol illustrates a beta-adrenoceptor agonist activity in large arteries. Since large artery compliance is impaired in hypertension, dilevalol may afford a vasular protective action for known risk factors for evolving systemic arterial disease.

Animals↗

PubMed1987

Effects of spiraprilic acid, an angiotensin converting enzyme inhibitor, on large artery compliance in anesthetized dogs.

The present study examined the actions of spiraprilic acid, a new non-sulfhydryl angiotensin converting enzyme (ACE) inhibitor upon aortic compliance (AC) in anesthetized dogs. Enalaprilic acid was examined for comparative purposes. AC was determined via sonomicrometric determination of the ratio of aortic systolic-diastolic diameter (mm) and arterial pulse pressure (mmHg). One AC unit (ACU) equals 10(-3) mm/mmHg. In non-thiazide pretreated animals, spiraprilic acid (1 mg/kg i.v.), caused a sustained hypotensive response of 21 +/- 3 mmHg (P less than .05). At the same time, aortic systolic and diastolic dimensions were reduced from basal values of 8.17 +/- 0.45 and 7.95 +/- 0.40 mm by 0.19 +/- 0.07 (P less than .05) and 0.29 +/- 0.10 mm (P less than .05), respectively. The aortic systolic-diastolic dimension rose significantly by 0.10 +/- 0.01 mm. Since pulse pressure was unchanged, AC rose from a basal value of 4.6 +/- 0.8 ACU by 1.7 +/- .3 ACU (P less than .05). Similar effects were observed with enalaprilic acid. In dogs pretreated orally with 5 mg/kg hydrochlorothiazide (HCTZ) twice daily for 3 days, spiraprilic and enalaprilic acids caused slightly greater falls in blood pressure (34 +/- 7 and 30 +/- 4 mmHg, respectively) than in nonpretreated dogs. However, the onset of the hypotension effect was more rapid for both ACE inhibitors in HCTZ-pretreated dogs. Effects of spiraprilic and enalaprilic acid upon aortic dimensions were similar to those observed in non-HCTZ pretreated animals. The data illustrate that the ACE inhibitors spiraprilic and enalaprilic acids not only lower blood pressure but also enhance large artery compliance.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed1987

Antihypertensive, hemodynamic and autonomic profile of a new angiotensin converting enzyme inhibitor, SCH 33844 (spirapril).

SCH 33844 is a new, potent and long-acting inhibitor of angiotensin converting enzyme (ACE). Antihypertensive, hemodynamic and autonomic actions of SCH 33844 were examined in the present series of experiments. Oral administration of 0.3-30 mg/kg reduced blood pressure of spontaneously hypertensive rats. The magnitude of the response was significantly enhanced by pretreatment of the animals with hydrochlorothiazide. Blood pressure remained significantly depressed 24 hr following doses of 3 and 10 mg/kg. Administration of SCH 33844 (3 mg/kg) twice daily to nonpretreated rats or once daily to diuretic-pretreated animals for 5 days resulted in a progressive decrease in blood pressure. The compound did not reduce blood pressure in nephrectomized rats demonstrating the dependence of its action on renal renin. SCH 33844 (1-10 mg/kg orally) also produced dose-related decreases in pressure in diuretic-pretreated conscious normotensive dogs. However, only a small fall in pressure occurred in non-pretreated dogs. Hemodynamic actions were examined in anesthetized dogs. SCH 33844 (1 mg/kg i.v.) reduced blood pressure, increased cardiac output and caused a large fall in peripheral resistance. Autonomic actions were assessed in pithed rats. The compound (10 mg/kg orally) tended to decrease pressor responses to sympathetic activation and to i.v. norepinephrine. This profile is probably due, at least in part, to vasorelaxation following suppression of angiotensin II generation. In conclusion, SCH 33844 is a potent, long-lasting antihypertensive agent which reduces peripheral vascular resistance and possesses only slight autonomic effects.

Adrenergic Agonists↗

PubMed1987

Comparative renal effects of calcium channel blockers in conscious spontaneously hypertensive rats.

Five calcium channel blockers with diverse chemical structures were studied for potential renal selectivity after oral administration of a single dose to conscious spontaneously hypertensive rats. Nitrendipine (3 and 10 mg/kg) and diltiazem (30 and 100 mg/kg) caused significant increases in sodium and water excretion. In comparison, prenylamine (100 and 300 mg/kg) and flunarizine (100 and 300 mg/kg) failed to augment sodium and water excretion. Verapamil caused significant natriuresis only at 30 mg/kg. These data suggest that the diuretic and natriuretic action is not a common property of all calcium channel blockers. Pretreatment with SCH 23390 (20 mg/kg), a dopamine DA1 antagonist, selectively attenuated the diuresis and natriuresis induced by high doses of diltiazem (100 mg/kg) and nitrendipine (10 mg/kg) without blocking the renal responses to hydrochlorothiazide (1 mg/kg). Similarly, reserpinization abolished the renal but not the hypotensive action of diltiazem. Pretreatment with indomethacin (10 mg/kg), a cyclooxygenase inhibitor also significantly attenuated the diuresis and natriuresis elicited by diltiazem (100 mg/kg). These data suggest that intact dopamine and prostaglandin systems in the kidney are required for optimal expression of the renal effects of diltiazem and nitrendipine.

Animals↗

PubMed1987

Angiotensin converting enzyme inhibitory activity of SCH 33844 (spirapril) in rats, dogs and monkeys.

SCH 33844 is a new non-sulfhydryl-containing angiotensin converting enzyme (ACE) inhibitor. SCH 33844 diacid inhibited hydrolysis of the synthetic substrate hippuryl-histidyl-leucine by rabbit lung ACE in vitro with an IC50 (concentration inhibiting enzyme by 50%) of 0.81 nM. The ester was 83 times less active. Intravenous administration of SCH 33844 and its diacid inhibited pressor responses to angiotensin I (AI) in anesthetized rats with calculated ID50's of 16 and 8 micrograms/kg, respectively. Oral administration of SCH 33844 (0.03-1 mg/kg) inhibited AI pressor responses in conscious rats with a duration of 24 hr at the highest dose. The diacid was inactive. Intravenous administration of SCH 33844 (100-1000 micrograms/kg) or its diacid (30 micrograms/kg) to anesthetized dogs inhibited AI pressor activity and potentiated the depressor response to bradykinin. SCH 33844 inhibited AI responses in conscious dogs following oral administration of 0.3-3 mg/kg. Oral administration of SCH 33844 (1 mg/kg) to conscious monkeys inhibited AI pressor responses for the 4 hr duration of study. In conclusion, SCH 33844 is a potent, orally effective ACE inhibitor in rats, dogs and monkeys.

Angiotensin I↗

PubMed1986

A post-calcium site of action for HA1004, a novel vasculorelaxant.

The novel vasorelaxant HA1004 [N-(2-guanidinoethyl)-5-isoquinolinesulfonamide] was investigated with regard to its effects on transmembrane Ca2+ movement in relation to tension development in the rabbit aortic strips. The contractile responses to KCl (40 mM) and norepinephrine (3 X 10(-7) M) were inhibited by HA1004 (1 and 3 X 10(-5) M) (49-78%), whereas the increases in 45Ca efflux (which reflects increases in cytosolic Ca2+ levels) were not affected. Moreover, HA1004 (1 and 3 X 10(-5) M) did not significantly affect 45Ca influx due to KCl stimulation. While HA1004 at 10(-5) M had no effect on norepinephrine-induced 45Ca influx, the drug at 3 X 10(-5) M showed significant inhibition. Based on this and previously reported work, it is concluded that HA1004 inhibits contraction mainly through uncoupling of the Ca-tension relations in vascular smooth muscle.

Animals↗

PubMed1986

The effects of atriopeptin II on calcium fluxes in rabbit aorta.

Effects of atriopeptin II (AP II) at 10(-7) M on the 45Ca flux and contractile responses to vasoconstrictors including norepinephrine (NE), angiotensin II (angio II) and high K were studied in isolated rabbit aortic strips. Augmentation of 45Ca efflux from aorta in normal physiological saline (PSS) due to NE and angio II each at 3 X 10(-7) M was greatly inhibited by AP II, suggesting that stimulated increase in cytosolic Ca2+ was suppressed. In contrast, the 45Ca efflux responses to KCl (20 and 40 mM) were not affected by AP II. Furthermore, the marked inhibition of contractile responses to NE (-58%) and angio II (-57%) by AP II was accompanied by significant decreases in 45Ca influx, whereas AP II exhibited only a modest inhibition on KCl (40 mM)-induced contraction (-28%) without affecting the accompanying increase in 45Ca influx. The 45Ca efflux from aortae in Ca2+-free PSS due to NE was markedly diminished by AP II, suggesting impairment of intracellular Ca2+ release. With tissues in either a basal or post-stimulation state (tissue Ca2+ previously increased with KCl stimulation), AP II did not stimulate 45Ca efflux in Ca2+-free PSS, suggesting its lack of effect on Ca extrusion. It is concluded that AP II is preferentially antagonistic against vascular responses to NE and angio II vs. high K and that inhibition of Ca entry and release forms the primary basis of its potent vasorelaxant action against vasoconstrictors.

Angiotensin II↗

PubMed1986

Analysis of vascular responses in rat hindquarters arterial resistance vessels and veins in situ.

The venous compartment plays a critical role in circulatory control. The present series of experiments was conducted to assess simultaneously effects of vasoactive drugs on arterial resistance and venous capacitance vessels of the rat hindquarters perfused with physiological salt solutions (SS). Retrograde infusion of SS into rat hindquarters via the vena cava resulted in an increase in hindquarters venous pressure (Pv). The range of mean volumes required to increase Pv to 20 and 30 mm Hg was 1.7 +/- 0.1 to 2.9 +/- 0.4 and 3.8 +/- 0.3 to 6.9 +/- 0.3 ml, respectively, in various groups of rats during a control period. Perfusion of the hindquarters with an SS containing 80 mM K+ reduced the volume required to increase Pv to 20 and 30 mm Hg to 47 +/- 2 and 42 +/- 2% of control, respectively, indicating venoconstriction. K+ (80 mM) SS also increased aterial perfusion pressure (Pa; measured from a sidearm off of the inflow catheter) to 141 +/- 9 mm Hg, indicating arterial vasoconstriction. Arterial and venous responses to 80 mM K+ were attenuated markedly by perfusion with SS containing zero Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid, indicating dependence on extracellular Ca. Phentolamine (10(-5) M) attenuated the arterial and venous response to 80 mM K+, indicating an alpha adrenergic contribution. Arterial responses to 80 mM K+ were attenuated markedly by the Ca entry blockers nifedipine (10(-6) and 10(-5) M) and verapamil (10(-6) and 10(-5) M). In contrast, venous responses were not affected by nifedipine and were reduced slightly only at the high concentration of verapamil.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Phorbol dibutyrate contractions in rabbit aorta: calcium dependence and sensitivity to nitrovasodilators and 8-BR-cyclic GMP.

Phorbol esters activate protein kinase C and induce contraction in vascular smooth muscle. The role of Ca and the sensitivity of this response to nitrovasodilators were evaluated in rabbit aortic rings. Phorbol dibutyrate (PDB) (0.01-10 microM) elicited a concentration-dependent contraction of rabbit aortic rings. Responses to PDB in a salt solution (SS) containing 2.54 mM CaCl2 were not significantly different from those in SS containing 0 Ca and 2 mM ethylene glycol bis(beta-aminoethyl ether)-N,N'-tetraacetic acid. Contractions to PDB (1 microM) in zero Ca SS were not reduced by depletion of the norepinephrine-sensitive pool of intracellular Ca. The Ca entry blockers verapamil (100 microM) and nifedipine (100 microM) did not affect PDB (1 microM) responses. Nitroprusside (0.1-10 microM) and nitroglycerin (0.1-10 microM) inhibited PDB contractions in both normal SS and Ca-free SS. 8-Br-cyclic GMP (100 microM) also inhibited PDB responses. Effects of PDB on 45Ca fluxes were evaluated in separate experiments. PDB (1 and 10 microM) elicited contraction, but no change in 45Ca uptake or efflux. In contrast KCl (80 mM) and norepinephrine (10 microM) elicited an increase in both influx and efflux, reflecting a rise in cytosolic Ca. The data suggest that PDB-induced contractions in rabbit aorta are independent of extracellular Ca and are not associated with a rise in cytosolic Ca as detected by calcium flux studies.(ABSTRACT TRUNCATED AT 250 WORDS)

8-Bromo Cyclic Adenosine Monophosphate↗

PubMed1986

AGEPC, a vasodilator phospholipid with profound circulatory actions.

Acetyl-glyceryl-ether-phosphoryl-choline (AGEPC) is a potent platelet activating factor which induces profound circulatory changes. AGEPC is synthesized in a variety of cell types including platelets, neutrophils, macrophages, basophils and endothelial cells. Biological responses include platelet activation, neutrophil activation, release of arachidonic acid metabolites and systemic anaphylaxis. Circulatory responses to AGEPC were evaluated in the present investigation. Intravenous administration of AGEPC (30 micrograms/kg/min) to anesthetized dogs reduced blood pressure, cardiac output, myocardial contractile force, renal blood flow and glomerular filtration. Intracoronary administration of AGEPC (0.3-3 micrograms) reduced blood pressure, coronary blood flow, and myocardial contractile force. Administration of AGEPC into the femoral vascular bed increased femoral artery blood flow. The data suggest that the circulatory response to AGEPC in the dog is complex and depends on the site of administration. The predominant response is hypotension mediated at least in part through myocardial depression. Intramuscular injection of AGEPC (10-30 micrograms/kg) to conscious spontaneously hypertensive rats (SHRs) reduced systemic blood pressure and increased heart rate. In pithed rats, AGEPC decreased pressor responses to sympathetic stimulation, angiotensin II and phenylephrine. Chronotropic responses were unchanged. Thus, antihypertensive doses of AGEPC reduced pressor responsiveness nonspecifically, but do not affect pre- or post-junctional adrenergic mechanisms. High concentrations of AGEPC (100 microM) relaxed phenylephrine contracted rabbit aortic rings. Relaxation was dependent on an intact endothelium. Lyso-GEPC produced similar actions. In light of the low potency of AGEPC and the activity of lyso-GEPC, physiological significance to endothelium dependent relaxation by AGEPC in rabbit aortic rings is unlikely. The physiological role of AGEPC in circulatory homeostasis is unclear at present. AGEPC may play a hypotensive role in some forms of experimental hypertension. In addition, AGEPC may mediate part of the circulatory derangements associated with cardiac anaphylaxis. Lastly, AGEPC may be involved in circulatory control during states of platelet and/or neutrophil activation such as myocardial ischemia and shock.

Animals↗

PubMed1985

The role of Na+-K+ -ATPase in the vasorelaxant actions of synthetic atrial natriuretic factor.

The present study evaluated the role of Na+-K+ -ATPase stimulation in the relaxant response to synthetic atrial natriuretic factor (atriopeptin II; ANF) in norepinephrine (0.18 microM)-contracted rabbit aorta. ANF (10(-10)-10(-7) M) produced a concentration-related relaxation of NE-contracted aortic rings. The calculated concentration required to produce 50 per cent relaxation (EC50) was 5 +/- 3 X 10(-9) M. ANF-induced relaxation was significantly attenuated by ouabain (30 microM). Likewise, ANF (10(-7) and 5 X 10(-9) M) elicited significantly less relaxation of aortic rings contracted with norepinephrine in a physiological salt solution containing zero KCl. Nitroprusside-induced relaxation also was attenuated by ouabain and in zero KCl salt solution. The data suggest that synthetic ANF induces relaxation in rabbit aortic rings by a ouabain and KCl sensitive mechanism, presumably Na+-K+ -ATPase.

Animals↗