Hypotensive Effects of the Crotalus Durissus Cascavella Venom: Involvement of NO

Crotalus durissus cascavella is a snake native of northeastern Brazil. The aim of the study was to investigate the effects of C. d. cascavella venom on rat mean arterial pressure and vascular reactivity in the mesenteric vascular bed. The venom evoked a dose-dependent decrease in mean arterial pressure, cardiac and respiratory frequency with increased plasma nitrite levels. L-NAME (10 mg/kg) blunted both the hypotension and increased nitrite production observed after the venom administration. To investigate the effects of C. d. cascavella in resistance vessels, the vascular mesenteric bed was studied, and the results suggested that the hypotensive effect of the venom is not dependent on a direct vasodilatory activity. In conclusion, C. d. cascavella venom presented indirect hypotensive effects with the involvement of nitric oxide.

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Effects of the enantiomers of a new dihydropyridine derivative, S12968 and S12967, on renal functions in rats

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y93-127 ◽

1993 ◽

Vol 71 (10-11) ◽

pp. 848-853

Author(s):

José M. López-Novoa ◽

Inmaculada Montañés

Keyword(s):

Blood Flow ◽

Renal Function ◽

Glomerular Filtration Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Glomerular Filtration ◽

Renal Blood Flow ◽

Filtration Rate ◽

Renal Plasma Flow ◽

Hypotensive Effect

The aim of this study was to evaluate the effects of the two enantiomers of a new dihydropyridine, S12967 and S12968, on rat renal function. Male Wistar rats were injected intravenously with saline, S12967, or S12968 (0.1, 0.3, or 1 mg/kg body weight). Urinary flow, glomerular filtration rate, renal plasma flow, urinary sodium, potassium, and calcium excretions, mean arterial pressure, and renal vascular resistance were determined before and every 30 min up to 180 min after administration of the tested substance. The levogyre enantiomer S12968, at a dose of 0.3 mg/kg, induced a 4-fold increase in urinary sodium excretion, without significant or with minor changes in glomerular filtration rate, renal plasma flow, or renal blood flow. The hypotensive effect was small and nonsignificant. At 1 mg/kg, S12968 caused a profound hypotensive effect that impaired the renal function, induced marked oliguria, and decreased glomerular filtration rate and renal blood flow to almost negligible values. The dextrogyre enantiomer S12967 had much less effect on renal function. These data showing specific stereoselective renal effects are in agreement with pharmacological studies that have demonstrated that S12968 possesses a higher affinity for the dihydropyridine-binding site than its dextrogyre enantiomer, S12967.Key words: Ca channel antagonists, dihydropyridine, glomerular filtration rate, renal blood flow, natriuresis, mean arterial pressure.

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Effects of althesin and urethan-chloralose on neurohumoral cardiovascular regulation

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1989.256.3.r757 ◽

1989 ◽

Vol 256 (3) ◽

pp. R757-R765 ◽

Cited By ~ 5

Author(s):

J. E. Faber

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Vascular Reactivity ◽

Pressor Response ◽

Cardiovascular Effects ◽

Plasma Renin ◽

Cardiovascular Regulation ◽

Pulse Interval ◽

Base Line

The cardiovascular effects of althesin (ALT) and urethan-chloralose (UC) anesthesia were compared in conscious, chronically instrumented rats. Althesin had no effect on arterial pressure or base-line resistance in the renal, superior mesenteric, and hindquarters vasculatures but increased heart rate. In contrast, UC decreased arterial pressure, heart rate, and mesenteric resistance. Although UC attenuated depressor responses to nitroglycerin, neither anesthetic significantly altered regional vascular reactivity to intravenous phenylephrine and nitroglycerin. The cardiac chronotropic baroreflex was examined by comparing the slope of the curves relating maximal changes (delta) in heart rate (pulse interval) that occurred at the point coinciding in time with the maximal changes in mean arterial pressure produced by phenylephrine and nitroglycerin. Neither anesthetic significantly altered the baroreflex slope (delta pulse interval/delta mean arterial pressure) for pressor and depressor stimuli. Both anesthetics attenuated the sympathoexcitatory response to cerebroventricular angiotensin II, although ALT had less of a depressive effect (pressor response during ALT and UC = 65 and 30%, respectively, of conscious). Plasma renin activity (PRA) and the hemodynamic response to peripheral angiotensin-receptor antagonism were significantly increased (PRA by almost 6-fold) during UC, whereas ALT was without effect. Similarly, UC but not ALT induced vasopressin-dependent vascular tone. Ganglionic blockade indicated that peripheral neurogenic tone was not altered by ALT anesthesia. These data suggest that althesin produces fewer hemodynamic disturbances than urethan-chloralose and largely maintains cardiovascular regulation intact.

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Aminoguanidine ameliorates splanchnic hyposensitivity to glypressin in a haemorrhage-transfused rat model of portal hypertension

Clinical Science ◽

10.1042/cs0950629 ◽

1998 ◽

Vol 95 (5) ◽

pp. 629-636 ◽

Cited By ~ 8

Author(s):

Chi-Jen CHU ◽

Fa-Yauh LEE ◽

Sun-Sang WANG ◽

Full-Young CHANG ◽

Han-Chieh LIN ◽

...

Keyword(s):

Nitric Oxide ◽

Portal Hypertension ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Portal Vein ◽

Rat Model ◽

Portal Pressure ◽

Hypotensive Effect ◽

Portal Vein Ligation ◽

Nitric Oxide Synthase Inhibitor

1.Hyposensitivity to vasopressin is a well-documented phenomenon in animals with portal hypertension and patients with cirrhosis subjected to haemorrhage. Excessive formation of nitric oxide is at least partly responsible for the vascular hyporesponsiveness to vasoconstrictors observed in experimental portal hypertension or in rats with haemorrhagic shock. This study investigated whether addition of aminoguanidine, a preferential inducible nitric oxide synthase inhibitor, to glypressin (a long-acting vasopressin analogue) could enhance its portal hypotensive effect in portal-hypertensive rats with bleeding. 2.Portal hypertension was induced by partial portal vein ligation. Fourteen days after operation, systemic and portal haemodynamics were measured in stable or bleeding portal vein-ligated rats receiving intravenous glypressin (0.07 ;mg/kg) or aminoguanidine (70 ;mg/kg) followed by glypressin infusion. In rats with a hypotensive haemorrhage, 4.5 ;ml of blood was withdrawn and 50% of the withdrawn blood was reinfused before the administration of glypressin or aminoguanidine. 3.Glypressin resulted in a significantly greater decrease in portal pressure in portal vein-ligated rats without bleeding than in those with bleeding (P< 0.001). In contrast, glypressin induced similar changes in mean arterial pressure between the two groups (P> 0.05). The addition of aminoguanidine significantly potentiated the portal-hypotensive effect of glypressin in bleeding portal vein-ligated rats (P< 0.005) without an effect on the changes in mean arterial pressure induced by glypressin infusion (P> 0.05). 4.Splanchnic hyposensitivity to glypressin exists in a haemorrhage-transfused rat model of portal hypertension. This hyposensitivity can be ameliorated by the administration of aminoguanidine.

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Spinal actions of substance P analogues on cardiovascular responses in the rat: a structure–activity analysis

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y87-069 ◽

1987 ◽

Vol 65 (3) ◽

pp. 412-418 ◽

Cited By ~ 5

Author(s):

Réjean Couture ◽

Alka Gupta ◽

René Kérouac ◽

Emanuel Escher ◽

Domenico Regoli

Keyword(s):

Heart Rate ◽

Amino Acid ◽

Mean Arterial Pressure ◽

Substance P ◽

Arterial Pressure ◽

Cardiovascular Effects ◽

Cardiovascular Responses ◽

Hypotensive Effect ◽

Intrathecal Administration ◽

Substance P Analogues

Ten substance P (SP) analogues were tested for their effects on mean arterial pressure and heart rate following intrathecal administration in the pentobarbital anaesthetized rat. The 10 analogues are [D-Pro4,D-αNpa7,9,10]SP(4–11) (A-I),(D-αNpa7,9,10]Sp (A-II);[D-Trp7,9,10]SP (A-III),[D-Pro4,D-Npa7,9, Phe11]SP(4–11) (A-IV),D-Pro4, D-βNpa7,D-αNpa9,D-Phe11]SP(4–11) (A-V), [D-Pro4,Lys6,D-Trp7,9,10, Phe11]SP(4–11) (A-VII),[D-Pro4,D-Trp7,9,10,Phe11]SP(4–11) (A-X),[D-Pro4,D-Trp7,9,10, Trp11]SP(4–11) (A-VIII),[D-Trp7,9,10, Trp11]SP (A-IX), and [D-Pro4,D-Phe7,9,10, Phe11]SP(4–11) (A-X). At 6.5 nmol, the analogues containing the amino acid D-Npa (A-I, A-II, A-IV, and A-V) or D-Phe (A-X) in positions 7, 9, or 10 or SP or its C-terminal octapeptide are devoid of the long-lasting cardio- and vaso-depressor effects, which are otherwise seen with analogues containing the amino acid D-Trp (A-III, A-VI, A-VII, A-VIII, and A-IX) in the same positions. Some of the analogues containing D-Npa maintain the initial hypotensive effect seen with SP while the analogue containing D-Phe produces only a small hypertensive response. The 10 analogues when tested at a dose that failed to alter basal mean arterial pressure and heart rate did not block the cardiovascular responses elicited by SP and no cross desensitization was observed between SP and these analogues. It appears that these SP analogues exert cardiovascular effects in the rat spinal cord probably without interacting with SP receptors.

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Natriuretic response to homologous heart extract in aglomerular toadfish

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1987.252.6.r1055 ◽

1987 ◽

Vol 252 (6) ◽

pp. R1055-R1058 ◽

Cited By ~ 3

Author(s):

J. Lee ◽

R. L. Malvin

Keyword(s):

Heart Rate ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Hypotensive Effect ◽

Systemic Hemodynamic ◽

Water Excretion ◽

Natriuretic Factor ◽

Muscle Extract ◽

Renal Responses ◽

Saline Vehicle

Although the renal effects of the atrial natriuretic factor (ANF) have been widely investigated, the mechanism of its natriuretic and diuretic effect is still controversial. The purpose of this study was to investigate whether ANF has a specific tubular action distinct from any renal or systemic hemodynamic effects. Renal responses to homologous heart extract (HE) or synthetic ANF were examined in the aglomerular toadfish. A significant natriuresis and diuresis were observed following an intra-arterial injection of either HE (amount derived from 1 heart) or ANF (atriopeptin III, 20 micrograms). However, neither affected urinary excretion of K+. Synthetic ANF did not alter the excretion of Mg2+ or Ca2+. In addition HE showed a hypotensive effect, and ANF did not alter the mean arterial pressure significantly. Neither HE nor ANF affected heart rate. Injection of skeletal muscle extract or saline vehicle alone was without effect on renal function, mean arterial pressure, or heart rate. These results support the hypothesis that ANF has a specific tubular action to increase urinary Na+ and water excretion. The presence of a natriuretic factor was demonstrated in the heart of the fish.

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Carotid chemoreceptors influence arterial pressure in intact and aortic-denervated rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1992.262.4.r677 ◽

1992 ◽

Vol 262 (4) ◽

pp. R677-R683 ◽

Cited By ~ 22

Author(s):

K. G. Franchini ◽

E. M. Krieger

Keyword(s):

Mean Arterial Pressure ◽

Arterial Pressure ◽

Carotid Body ◽

Hypotensive Effect ◽

Carotid Chemoreceptors ◽

Arterial Pressure Variability ◽

Before And After ◽

The Mean

The objective of the present study was to analyze the role of the arterial chemoreceptors in arterial pressure alterations produced by sinoaortic denervation (SAD) in rats. The mean arterial pressure during 2 h of continuous computerized beat-to-beat recordings was higher after aortic denervation (AD; 130 +/- 2 and 124 +/- 3 mmHg, respectively), lower after sinus denervation (SD; 101 +/- 1 and 101 +/- 3 mmHg), and remained unaltered after SAD (121 +/- 3 and 108 +/- 2 mmHg) 1 and 20 days after denervation compared with control rats (114 +/- 1 mmHg). Hypotensive effect of SD was confirmed when arterial pressure was recorded in the same animal before and after SD (from 112 +/- 2 to 103 +/- 2 mmHg). A similar effect was observed after isolated carotid body artery (CBA) ligation (from 114 +/- 3 to 104 +/- 3 mmHg). Furthermore, CBA ligation attenuated by 13% the hypertension after AD (from 136 +/- 2 to 118 +/- 3 mmHg). Bradycardic response to phenylephrine and arterial pressure variability were markedly altered by SAD and AD but remained normal after SD. In contrast, the chemoreflex (intravenous KCN) was abolished after SAD, SD, and CBA ligation but was preserved after AD. These data suggest that the arterial pressure alteration produced by SAD in rats represents the net effect of the abolition of inhibitory (baroreceptor deafferentation) and excitatory (chemoreceptor deafferentation) influences on the arterial pressure.

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Effect of dietary sodium intake on the pressor reactivity to angiotensin II in rats with experimental cirrhosis of the liver

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-243 ◽

1989 ◽

Vol 67 (12) ◽

pp. 1506-1511 ◽

Cited By ~ 7

Author(s):

L. M. Villamediana ◽

Angel L. García-Villalón ◽

Carlos Caramelo ◽

José M. López-Novoa

Keyword(s):

Angiotensin Ii ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Vascular Reactivity ◽

Sodium Intake ◽

Pressor Response ◽

Experimental Cirrhosis ◽

High Sodium ◽

Sodium Diet ◽

High Sodium Diet

The present experiments were designed to evaluate vascular reactivity to angiotensin II in rats with experimental cirrhosis of the liver (induced with CCl4 and phenobarbital) before ascites appearance. The systemic pressor response to angiotensin II in conscious animals and the contractile effect of angiotensin II in isolated femoral arteries were studied. In addition, the effect of high sodium intake on these parameters was also analyzed. Both renin and aldosterone plasma concentrations were similar in control and cirrhotic rats on the normal or on the high sodium diet. Basal mean arterial pressure was higher in control rats than in cirrhotic rats on the normal sodium (116 ± 4 vs. 101 ± 4 mmHg (1 mmHg = 133.3 Pa),p < 0.05) or on the high sodium diet (118 ± 7 vs. 98 ± 6 mmHg). No differences in plasma renin activity or plasma aldosterone were found between control and cirrhotic rats. Upon injection of angiotensin II, control rats show a dose-dependent increase in mean arterial pressure which is higher in high sodium than in normal sodium rats. Cirrhotic rats showed a lower hypertensive response to angiotensin II than their corresponding control rats. In addition, no difference between pressor responses to angiotensin II was observed when normal sodium and high sodium cirrhotic rats were compared. On application of angiotensin II, femoral arteries of control and cirrhotic rats exhibited a dose-dependent contraction. However, maximal contraction was higher in high sodium control rats (145 ± 12 mg) than in normal sodium control rats (99 ± 6 mg, p < 0.05). No significant differences between control and cirrhotic rats on either sodium diet were observed. In conclusion, cirrhotic, nonascitic rats showed an impaired pressor response to angiotensin II that is more marked after a high sodium diet. These differences are not due to changes in the contractility of peripheral arteries to angiotensin II.Key words: angiotensin II, liver cirrhosis, sodium intake, mean arterial pressure, vascular reactivity.

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