Biomedical subjects

R Tabrizchi

Publications and source records attributed to R Tabrizchi.

At least 37 records · Page 2Linked to original sources

PubMed1995

Vasodilatation produced by adenosine in isolated rat perfused mesenteric artery: a role for endothelium.

Adenosine and adenosine triphosphate (ATP) induced vasodilatation was studied in isolated rat perfused mesenteric artery at constant flow. Decrease in perfusion pressure was measured after induction of tone by continuous infusion with phenylephrine (5-7 microM). Adenosine and ATP caused dose-dependent vasodilation. Following infusion with selective A2 adenosine receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX) (10 microM), or non-selective adenosine receptor antagonist, theophylline (30 microM), vasodilation produced by adenosine were significantly reduced at lower doses. Responses to adenosine were not affected by pretreatment of tissues with either the P2-purinoceptor desensitizing agent, alpha, beta methylene ATP (30 microM), or the P2-purinoceptor antagonist, suramin (10 microM). In contrast, both alpha, beta methylene ATP and suramin significantly attenuate relaxation produced by ATP. Further, it was found that relaxation elicited by either adenosine or ATP was not significantly affected by the presence of glibenclamide (30 microM). Vasodilatation induced by adenosine and ATP was greatly reduced in denuded arteries but more so for ATP than adenosine. It is concluded that adenosine-mediated vasodilatation may hardly be due to the stimulation of A2 adenosine receptors and is strongly dependent on the presence of functional endothelium whereas ATP-mediated vasodilator responses were mediated via the activation of P2-purinoceptors and appeared to be entirely dependent upon the presence of functional endothelium. Further, vasodilator responses to neither adenosine nor ATP were sensitive to inhibition by the potassium channel blocker glibenclamide, in isolated mesenteric perfused bed. This would imply that ATP-sensitive potassium channels were not involved in adenosine and ATP mediated vasodilatation.

Adenosine↗

PubMed1995

Effects of calcium channel antagonists and pertussis toxin on noradrenaline-induced contractions in pulmonary artery from pulmonary hypertensive rats.

The influence of calcium channel antagonists, felodipine and cadmium, as well as pertussis toxin on noradrenaline-induced contractions in pulmonary artery rings from rats with pulmonary hypertension induced by monocrotaline (MCT) were examined. MCT-treated rats had pulmonary hypertension, right ventricular hypertrophy and lung oedema, as compared to corresponding vehicle-treated rats. The MCT-treated animals did not have polycythemia as compared to vehicle-treated rats. Pre-treatment of pulmonary artery rings from MCT-treated rats with felodipine and cadmium significantly reduced the maximum response without altering the EC50 or the Hill coefficient of concentration-response curve to noradrenaline. In pulmonary artery rings from vehicle-treated rats, felodipine significantly increased the EC50 and reduced the maximum response and the Hill coefficient of the concentration-response curve to noradrenaline. In contrast, cadmium did not alter these parameters in pulmonary artery rings from vehicle-treated rats. Pertussis toxin did not affect noradrenaline-induced contractions in pulmonary artery rings from vehicle- or MCT-treated rats. Felodipine, cadmium and pertussis toxin were ineffective in inhibiting noradrenaline-induced contractions in aortic rings from either vehicle- or MCT-treated rats. Our results can be interpreted to indicate that alteration to voltage operated, felodipine-sensitive, calcium channels as well as, cadmium-sensitive sites contribute to the changes observed in the functional behavior of pulmonary blood vessels from pulmonary hypertensive rats.

Animals↗

PubMed1995

Influence of nonpeptide angiotensin II receptor antagonist, losartan, on neurogenic vasoconstriction.

The influence of the nonpeptide angiotensin antagonist losartan on andrenergic/purinergic cotransmission in pithed rat preparation before and after treatment with prazosin (alpha 1-antagonist), rauwolscine (alpha 2-antagonist), and/or the P2x desensitizing agent alpha, beta-methylene ATP (mATP) was examined. Stimulation of the spinal sympathetic outflow (T6-T8) through the pithing rod (1.0-cm electrode) at supramaximal voltage, 0.05-ms pulses, at different frequencies (1-40 Hz) evoked biphasic responses. Changes in diastolic blood pressure (DBP) were assessed at the early peak after the 1.0-train. The vasopressor responses to sympathetic nerve stimulation were partially blocked by prazosin, rauwolscine, mATP, and losartan. Administration of prazosin or mATP but not rauwolscine as compared with losartan alone could further reduce vasopressor responses to sympathetic nerve stimulation. In rats treated with losartan and either prazosin or rauwolscine, administration of mATP further reduced vasoconstrictor responses to sympathetic nerve stimulation. In contrast, rauwolscine did not further reduce vasoconstriction due to sympathetic nerve stimulation in rats that had received losartan and prazosin combined. Furthermore, the inhibitory actions of mATP were significantly greater in rats that had received losartan and prazosin as compared with rats that received losartan and rauwolscine. The results indicate that losartan in vivo is most effective in inhibiting nerve-mediated alpha 2-adrenoceptor responses as opposed to either alpha 1-adrenoceptor or P2x-purinoceptor responses.

Adenosine Triphosphate↗

PubMed1995

The effects of losartan and captopril on vasopressor actions of cirazoline in the absence and presence of SZL-49 and nifedipine.

The effects of the nonpeptide angiotensin II receptor antagonist losartan and the angiotensin-converting enzyme inhibitor captopril on pressor responses to the selective alpha 1-adrenoceptor agonist cirazoline (10 ng/kg-3.0 mg/kg) in the pithed rat were compared. In addition, the effects of losartan and captopril on pressor responses to cirazoline were compared in the presence of the selective irreversible alpha 1-adrenoceptor antagonist SZL-49 (1-(4-amino-6,7-dimethoxy-2-quinazolinyl)-4-(2-bicyclo[2,2,2]octa-2,5- dienyl-carbonyl)-piperzine) and/or the Ca2+ channel antagonist nifedipine. Losartan (5.0 mg/kg) and captopril (3.0 mg/kg), as compared to saline, significantly lowered the blood pressure of intact, anaesthetized and pithed rats. Continuous infusion with vasopressin was used to restore the blood pressure of pithed rats pretreated with losartan or captopril to a level comparable to animals that had received saline. Losartan, captopril, nifedipine (1.0 mg/kg), and SZL-49 (10.0 mg/kg) antagonized the pressor actions of cirazoline, which displaced the dose-diastolic blood pressure response curve for the agonist to the right. Moreover, pressor responses to cirazoline were significantly reduced in rats that had received losartan and nifedipine in comparison to nifedipine alone. In contrast, in rats treated with nifedipine, further administration of captopril did not significantly reduce pressor responses to cirazoline as compared to nifedipine alone. Cirazoline-mediated pressor responses at all doses were significantly attenuated in rats treated with SZL-49 and either losartan or nifedipine combined as compared to SZL-49 alone. In contrast, only cirazoline-mediated pressor responses at lower doses were significantly reduced by pretreatment with a combination of SZL-49 and captopril as compared to SZL-49 alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1995

Effects of 8-bromoguanosine 3':5'-cyclic monophosphate on phenylephrine-induced phosphatidylinositol hydrolysis and contraction in rat caudal artery.

1. The effects of 8-bromoguanosine 3':5'-cyclic monophosphate (8-bromo-cyclic GMP) on phenylephrine-induced contractions and phosphatidylinositol (PI) hydrolysis were investigated in rat isolated caudal artery. The effects of the nucleotide were compared to those of felodipine, a dihydropyridine Ca2+ channel antagonist and ryanodine, a putative depletor of intracellular Ca2+ stores. The purpose of this investigation was to examine the regulatory effects of cyclic GMP on receptor-mediated signal transduction in vascular smooth muscle. 2. Phenylephrine induced a concentration-dependent increase in PI hydrolysis that reached a maximum at 10 microM phenylephrine. Pre-incubation with felodipine (10 nM) significantly reduced PI turnover, but did not affect basal hydrolysis. Similarly, removal of extracellular Ca2+ (2 mM ethylene glycol-bis(beta-amino-ethyl ether) N, N, N', N'-tetraacetic acid (EGTA)) blocked phenylephrine-induced PI hydrolysis, but did not affect basal turnover. In contrast, 8-bromo-cyclic GMP (10 microM) did not affect phenylephrine-induced PI hydrolysis, nor did it affect basal turnover. 3. Phenylephrine induced concentration-dependent contractions that were inhibited by each of 8-bromo-cyclic GMP (10 microM), felodipine (1 nM and 10 nM) and ryanodine (3 microM and 10 microM). In addition, removal of Ca2+ from the physiological salt solution (2 mM EGTA) completely abolished contractions elicited by phenylephrine. 4. Phenylephrine-induced contractions were not further affected by felodipine and 8-bromo-cyclic GMP applied concomitantly than by equivalent concentrations of felodipine alone. However, ryanodine and 8-bromo-cyclic GMP applied together significantly inhibited phenylephrine-induced contractions in comparison to ryanodine alone. 5 These results suggest that phospholipase C-activated PI hydrolysis in the rat caudal artery is dependent on extracellular Ca2+, mediated, in part, through dihydropyridine-sensitive Ca2+ channels.Inhibition of contraction by felodipine may be brought about through indirect inhibition of IP3 production and subsequent attenuation of intracellular Ca2+ release. 8-Bromo-cyclic GMP does not inhibit PI hydrolysis; it may regulate vascular smooth muscle contraction by inhibition of Ca2+ release from IP3-mediated intracellular stores, but it is unlikely that 8-bromo-cyclic GMP affects ryanodine-sensitive stores.

Animals↗

PubMed1994

Effects of chronic receptor blockade on excitation-contraction coupling in rat aortic rings.

The effects of an intracellular Ca2+ depletor (ryanodine), a Ca2+ channel antagonist (felodipine), a protein kinase C inhibitor (staurosporine) as well as caffeine, cholera and pertussis toxin have been examined on noradrenaline-induced contractions in aortic rings from rats pretreated i.v. with either saline or phenoxybenzamine for 7 days. Ryanodine (3 and 10 microM) was able to both potentiate and inhibit noradrenaline-evoked contractions in aortic rings from phenoxybenzamine-treated rats. However, ryanodine did not affect the concentration-response curves to noradrenaline in tissues from saline-treated rats. Further, felodipine (1 and 10 nM) and staurosporine (10 nM) inhibited noradrenaline-induced contractions in aortic rings from phenoxybenzamine- but not saline-treated rats. Pertussis toxin (100 ng/ml) also inhibited contractions produced by noradrenaline in rings from phenoxybenzamine- but not saline-treated rats. In contrast to these observations, both caffeine (1 mM) and cholera toxin (3 micrograms/ml) inhibited noradrenaline-evoked contractions in aortic rings from phenoxybenzamine- and saline-treated rats. The results suggest that chronic receptor blockade by phenoxybenzamine leads to alteration in alpha-adrenoceptor-mediated signal transduction in the aorta. The changes include alteration in Ca2+ handling at the plasmalemmal and intracellular levels, as well as an altered action of pertussis toxin-sensitive G-protein, but not of cholera toxin-sensitive G-protein.

Alkaloids↗

PubMed1994

Pressor responses to the alpha 1-adrenoceptor agonist cirazoline: effects of captopril, phenoxybenzamine and nifedipine.

We have examined the effects of captopril on pressor responses to the selective alpha 1-adrenoceptor agonist cirazoline in the pithed rat preparation following treatment with phenoxybenzamine and/or nifedipine. Pretreatment with captopril reduced the pressor responses to cirazoline and displaced the dose-response curve for this agonist to the right, significantly increasing the ED50 without altering the maximum response. Pretreatment with phenoxybenzamine accentuated the inhibitory actions of captopril and a combination of phenoxybenzamine and captopril significantly increased the ED50 without altering the maximum response. Administration of nifedipine in animals, which had already received phenoxybenzamine and captopril, led to a further displacement to the right of the cirazoline dose-response curve. The ED50 was found to be significantly increased and the maximum response was now significantly depressed. Captopril produced further additive inhibition with nifedipine and phenoxybenzamine of the vasoconstrictor effects of cirazoline. These data indicate, perhaps not surprisingly, that the cellular basis for the inhibitory effects of captopril is different from that of nifedipine and phenoxybenzamine, however, more importantly, that captopril may directly, or indirectly, inhibit receptor-operated cation channel mediated pressor responses.

Adrenergic alpha-Agonists↗

PubMed1994

The effects of perfusion rate and NG-nitro-L-arginine methyl ester on cirazoline- and KCl-induced responses in the perfused mesenteric arterial bed of rats.

1. The purpose of this study was to characterize the effect of NG-nitro-L-arginine methyl ester (L-NAME) on the perfusion rate/pressure relations, and on the pressor responses induced to cirazoline and KCl in isolated, perfused mesenteric arterial beds from normotensive and spontaneously hypertensive rats. 2. The basal perfusion pressure of arterial beds perfused with either physiological salt solution (PSS) or PSS containing 1% polyvinylpyrrolidone increased as the perfusion rate increased. L-NAME, in concentrations up to 100 microM, failed to alter the basal pressure regardless of the perfusion rate and viscosity; however, at 5 microM, it potentiated cirazoline-induced vasoconstriction at each of the perfusion rates. 3. L-NAME but not D-NAME caused a leftward shift of cirazoline concentration-response curves with a marked increase in the maximal response. The potentiating action of L-NAME was abolished in arterial beds perfused with a Ca(2+)-free physiological salt solution and also in beds denuded of endothelium by an infusion of distilled water for 5 min. 4. In endothelium-intact and -denuded preparations, L-NAME potentiated KCl pressor responses; the endothelium-independent potentiation of KCl pressor activity was stereospecific, time-independent and was not prevented by the presence of dexamethasone (0.5 microM) in the perfusion medium. However, L-NAME failed to potentiate vasoconstriction obtained to KCl in arterial beds denervated by cold storage (4-5 degrees C) for 2 days. 5. The absence of K+ in the perfusate did not inhibit the ability of L-NAME to potentiate alpha-adrenoceptor-mediated pressor responses, and nor did L-NAME inhibit KCl-induced vasodilatation in preconstricted arteries. It was thus concluded that L-NAME does not affect Na+/K(+)-ATPase activity. 6. No differences in the potentiating ability of L-NAME on either cirazoline- or KCl-mediated pressor responses were apparent between normotensive Sprague Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive (SHR) rats.7. Our data thus provide evidence that: the presence of a vasoconstrictor is required for basal nitricoxide (NO) release in the mesenteric arterial bed from either normotensive or spontaneously hypertensive rats; L-NAME causes potentiation of cirazoline- and KCl-induced vasoconstriction respectively by inhibiting endothelial and neuronal NO synthase(s). Furthermore, our data indicate that NO synthase activity is not impaired in the mesenteric arterial bed of spontaneously hypertensive rats.

Adrenergic alpha-Agonists↗

PubMed1993

Influence of intravenous infusion of ethanol on regional blood flow in conscious rats.

The effects of intravenous infusions of ethanol and saline (0.9% NaCl) on mean arterial pressure (MAP), heart rate (HR), total peripheral resistance (TPR), cardiac contractility (dP/dtmax) and systemic haemodynamics were studied in conscious, unrestrained rats by the radioactive microsphere technique. Saline (0.03 and 0.06 mL min-1 kg-1 for 12 min each dose) in the time-control group did not affect MAP, HR, TPR, dP/dtmax or vascular conductances in any organs or beds. While the low dose ethanol (2.4 mg min-1 kg-1) did not alter MAP, HR, TPR, systemic haemodynamics or dP/dtmax, the high dose (4.8 mg min-1 kg-1) slightly reduced MAP and TPR but did not affect HR, cardiac output or dP/dtmax. Both doses of ethanol vasodilated the intestine and spleen, but vasoconstricted the skin. The high dose caused additional vasodilatation in the heart and testes and the low dose also constricted the skeletal muscle bed. Our results show that ethanol, at non-hypotensive or slightly hypotensive doses, has marked vasodilator effects in the heart, intestine, spleen and testes.

Animals↗

PubMed1993

Possible equilibration of portal venous and central venous pressures during circulatory arrest.

The mean circulatory filling pressure technique has been used to assess total body venous tone. It involves measuring central venous pressure (CVP) at 5-8 s following circulatory arrest. This study examines if CVP and portal venous pressure (PVP) equilibrate when circulation is stopped by inflating a balloon implanted in the right atrium. CVP and PVP were measured in the control condition and after intravenous bolus injections of norepinephrine (NE, 1.6 microgram/kg), angiotensin II (ANG II, 1.3 microgram/kg), and isoproterenol (Iso, 0.5 microgram/kg) in conscious and pentobarbital-anesthetized rats. In conscious rats, CVP was similar to PVP after circulatory arrest under conditions of normal, elevated, or reduced vascular tone. In anesthetized rats, CVP was similar to PVP in the control condition and after intravenous bolus injection of NE and Iso but was less than PVP after the administration of ANG II. Therefore, mean circulatory filling pressure may not fully reflect total body venous tone in anesthetized, surgically stressed rats.

Angiotensin II↗

PubMed1993

Changes in vascular smooth muscle function in hypertension.

In a comparison of the spontaneously hypertensive rat (SHR) with Wistar-Kyoto (WKY) and Sprague Dawley (SD) rats, it was shown that pertussis toxin (PTX) lowers the blood pressure of the SH but not WKY or SD rats. Sympathetic nerve stimulation (SNS), via the pithing rod, the nitric oxide NO)-synthase inhibitor NW-Nitro-L-arginine methyl ester L-NAME) and the pressor response to infusion of AVP were also observed. The results indicate that a G-protein(s) population and/or function may be altered in the vascular smooth muscle of SH rats. This dysfunction may contribute to the heightened pressor responsiveness of the SHR vasculature to SNS and arginine vasopressin (AVP) and the increased sensitivity to the hypotensive effects of nifedipine. NO-synthase activity also appears to be increased in the SHR, suggesting that this increase should reflect a compensatory change due to the elevation of BP in SHR.

Animals↗

PubMed1992

Direct and indirect effects of angiotensin II on venous tone in conscious rats.

The direct and indirect effects of angiotensin II (ANGII) on mean arterial pressure (MAP) and mean circulatory filling pressure (MCFP), an index of body venous tone, were investigated in conscious rats. Dose-response curves of ANGII were constructed in control rats (Group I), rats pretreated with saralasin (competitive ANGII antagonist, Group II), with guanethidine (inhibitor of sympathetic postganglionic neurons. Group III), or the ganglionic blocker hexamethonium (Group IV) and rats given unilateral right adrenalectomy two days prior to the study (Group V). The infusion of single doses of ANGII in control, adrenalectomized, guanethidine-treated and hexamethonium-treated rats dose dependently increased MAP to similar maxima; ED50 value was increased by adrenalectomy but unaffected by guanethidine nor hexamethonium. The pressor effects of ANGII was almost completely abolished by saralasin. ANGII dose dependently increased MCFP in control rats. In hexamethonium-treated rats, ANGII also dose relatedly increased MCFP which reached similar maximum as that in control rats, but the ED50 value was reduced. Saralasin almost completely abolished the MCFP response. Both guanethidine and adrenalectomy reduced maximum MCFP response to ANGII, but neither altered the ED50 value. Our results show that the sympathetic nervous system contributed greater to the MCFP than MAP effects of ANGII. Both direct and indirect effects of ANGII are mediated via the activation of ANGII receptors that are susceptible to blockade by saralasin.

Angiotensin II↗

PubMed1992

Alpha-mediated vasoconstriction: transmembrane signalling and receptor reclassification.

Apparent differences in the usage of different calcium pools for the processes of excitation-contraction provides support for further sub-classification of the alpha-adrenoceptors in blood vessels. Presently we have addressed this question by assessing the routes of calcium utilization and the involvement of G-proteins in mediating vasoconstriction in situ.

Adrenergic alpha-Agonists↗

PubMed1992

Effects of drugs on body venous tone, as reflected by mean circulatory filling pressure.

The venous system is supremely important in the control of cardiac output. Drugs which affect the venous system have profound effects on haemodynamics. This review comments on the methods available for the determination of venous compliance, resistance, and unstressed volume and describes the mean circulatory filling pressure (MCFP) technique, its usefulness and limitations. The MCFP technique involves the measurement of central venous pressure during brief (5-7 s) circulatory arrest. Mathematically, MCFP is inversely proportional to vascular compliance while experimentally, it is a primary determinant of venous return. The MCFP technique provides a reproducible and relatively non-traumatic means for the estimation of body venous tone in conscious and anaesthetised animals. Drugs examined by this technique include alpha and beta adrenoceptor agonists and antagonists, ganglionic blockers, vasoactive peptides (endothelin, vasopressin, angiotensin, neuropeptide Y), and vasodilators (hydralazine, nitroprusside, glyceryl trinitrate, calcium antagonists, and MCI-154).

Animals↗

PubMed1992

The interrelationship between the effects of captopril and nifedipine on pressor responses elicited by selective alpha-adrenoceptor agonists in the pithed rat preparation.

The interrelationship between the effects of the angiotensin converting enzyme inhibitor captopril and the calcium channel antagonist nifedipine on alpha-mediated vasoconstriction elicited by the administration of the full and partial alpha 1-adrenoceptor agonists St 587 and cirazoline, respectively, and the alpha 2-adrenoceptor agonist B-HT 920 were examined in pithed normotensive rats. Treatment with captopril was found to attenuate pressor responses produced by the administration of either alpha 1- or alpha 2-adrenoceptor agonists, resulting in the displacement to the right of the agonist dose-response curves and significantly increasing the calculated ED50 values. The maximum response was unaltered and the calculated dose ratios for alpha-agonists in the presence or absence of captopril were found to be 3, 4.6, and 3.8 for B-HT 920, St 587, and cirazoline, respectively. In comparison, nifedipine displaced the dose-response curves for all three alpha-agonists to the right but only significantly increased the ED50 values for the partial alpha 1-agonist St 587 and the alpha 2-agonist B-HT 920, with the calculated dose ratios being 3.2 and 3.8, respectively. Following treatment with nifedipine, however, the maximum responses were significantly reduced. A combination of captopril and nifedipine did not result in any significant additive increase in the ED50 values compared to those obtained with captopril or nifedipine alone. However, the inhibition of the maximum response to B-HT 920 by a combination of captopril and nifedipine was additive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗

PubMed1992

A comparison of the effects of acute versus chronic administration of phenoxybenzamine on pressor responses elicited by the selective alpha 1-adrenoceptor agonist cirazoline in the pithed rat preparation.

The effects of nifedipine on the pressor responses to cirazoline were examined in the pithed rat preparation that had received either acute or chronic phenoxybenzamine treatment. Phenoxybenzamine was administered, i.v., to conscious rats, either acutely at 0.01, 0.03, and 0.1 mg/kg, 60 min prior to the commencement of the experiments or chronically at 0.1, 0.3, and 1.0 mg/kg, once daily for 7 days. Nifedipine was administered i.a. (1.0 mg/kg) after the animals had been pithed. The acute or chronic administration of phenoxybenzamine alone displaced the dose-response curve to cirazoline to the right in a dose-dependent manner, while reducing the slope function and maximum response to the agonist. The combined effects of acute phenoxybenzamine and nifedipine produced an additive inhibitory effect on the pressor response elicited by cirazoline, which was most apparent following the removal of receptor reserve by acute phenoxybenzamine. The inhibitory effects of nifedipine and chronically administered phenoxybenzamine were additive at the lower administered doses of the alkylating agent but, in contrast with the effects of acute phenoxybenzamine, the enhanced inhibitory effects of nifedipine were reduced following the removal of receptor reserve. These results indicate that the chronic administration of phenoxybenzamine reduces the additive inhibitory effects of nifedipine and phenoxybenzamine that were observed following the acute administration of phenoxybenzamine.

Adaptation, Physiological↗

PubMed1992

Actions of L- and D-arginine and NG-monomethyl-L-arginine on the blood pressure of pithed normotensive and spontaneously hypertensive rats.

We have examined the depressor effects of L- and D-arginine on the diastolic blood pressure of pithed normotensive Wistar (NW), Wistar-Kyoto (WKY) and spontaneously hypertensive (SH) rats after the administration of a single bolus injection of the nitric oxide synthase inhibitor, NG-monomethyl-L-arginine (L-NMMA). A single bolus intravenous injection of L-NMMA, 30 mg/kg, produced an increase in both the systolic and diastolic blood pressure of pithed rats. Injections of bolus doses, 1-300 mg/kg, of D-arginine did not lead to sustained reductions of the blood pressure in pithed NW rats although slight decreases in the blood pressure of WKY and SH rats were observed, and these transient effects of D-arginine appeared to be more pronounced in the WKY strain. Immediately following the bolus injections of the higher doses of D-arginine a transient decrease in both the systolic and diastolic pressure occurred. In contrast to the actions of D-arginine single bolus injections of L-arginine, 1-300 mg/kg, produced a dose-dependent sustained reduction in both the systolic and diastolic blood pressures of all rats. The threshold for the depressor actions of L-arginine was the same for NW, WKY and SH rats. The final dose of L-arginine (300 mg/kg), produced a significantly greater depressor effect in WKY and SH rats as compared to NW rats. The blood pressure remained elevated after the dose-response curve to D-arginine and, in order to determine whether D-arginine-treated rats are sensitive to the effects of other vasodilators and whether differences in vasoactive actions exist for vasodilators acting other than via nitric oxide synthesis, a dose-response curve to the calcium channel antagonist verapamil was constructed. Injections of verapamil, 0.1-1000 micrograms/kg, produced a dose-dependent reduction in blood pressure with no difference in either threshold or sensitivity to the actions of verapamil among the three strains of rats. Our results suggest that strain differences exist between the depressor actions of L-arginine and that it is possible that these differences may be due to an alteration in the endogenous levels of nitric oxide synthase and/or the activity of guanylate cyclase, however, no relationship to the hypertensive state of the spontaneously hypertensive rats was apparent.

Animals↗

PubMed1991

Influence of N omega-nitro-L-arginine methyl on pressor responses elicited by sympathetic nerve stimulation in pithed normotensive and hypertensive rats.

The effects of N omega-nitro-L-arginine methyl ester (L-NAME) were examined on pressor responses elicited by sympathetic nerve stimulation (SNS) in the pithed spontaneously hypertensive (SH) and Wistar-Kyoto (WKY) rats. Frequency-response curves (1-20 Hz) were carried out by using the pithing rod to stimulate the sympathetic chain. SNS produced an increase in the blood pressure of the pithed rats which was dependent on the frequency of the applied stimuli, however, a significantly greater increase was observed for the blood pressure of SH versus WKY rats. Bolus i.v. injections of L-NAME (0.03-1.0 mg/kg) augmented the increase in the blood pressure resulting from SNS. The potentiating effects of L-NAME displayed frequency as well as dose-dependency and the augmentation produced following the administration of L-NAME was greater in magnitude in the SH as compared to WKY rats. These differential effects of L-NAME in SH versus WKY rats suggest that the levels of L-arginine-derived nitric oxide are higher in the SH rats. Such an increase may reflect a compensatory response resulting from the elevated blood pressure of the SH rats.

Amino Acid Oxidoreductases↗