Regional Vascular Resistance Research Articles

Hind-limb/hind-quarter vascular resistance and blood flow changes: possible intrinsic renin–angiotensin system involvement

For many years there was a general belief that the enzyme renin, having been secreted into the circulation by the kidney in response to appropriate stimuli, initially generates the inactive decapeptide angiotensin I in the bloodstream. This is then converted to the biologically active octapeptide angiotensin II by angiotensin converting enzyme on or near, vascular surface receptors both in the lungs and in the organs supplied by the systemic circulation. The results of various investigations have, however, latterly led to the conclusion that the overall system is widely distributed throughout the vasculature with the local intracellular formation of angiotensin II. In this review the reckoned intrinsic renin–angiotensin activity in hind-limb/hind-quarter is discussed with particular regard to the widespread use of radioimmunoassay, together with a consideration of other factors, more especially ACE inhibition, affecting the relevant regional vascular resistance and blood flow.

Altered mRNA expression of ecNOS and iNOS in myometrium and placenta from women with preeclampsia

Preeclampsia is a syndrome involving dysfunction of vascular endothelium and imbalance between endothelium derived constricting and relaxing factors. Recent evidence suggests that endothelium-derived nitric oxide (NO) plays a role in the regulation of vascular resistance during normal pregnancy and preeclampsia. NO is a potent vasodilator and is generated by the catalytic action of nitric oxide synthases ecNOS and iNOS in myometrium and placenta. In this study mRNA expressions of ecNOS and iNOS were compared in myometrium and placenta. Biopsies were collected from women with preeclampsia (n=8) and normal pregnancies (n=12). ecNOS and iNOS mRNA levels were determined using RT-PCR and expressed as arbitrary units after correction for control GAPDH gene mRNA levels. The mRNA expression of ecNOS was significantly higher in both myometrium (p<0.05) and placenta (p<0.05) from women with preeclampsia compared to that in normal pregnancies, while the iNOS mRNA level was not altered in myometrium and lower in placenta (p<0.05) from women with preeclampsia. The higher ecNOS mRNA expression might be a compensatory response to an impaired vasodilatation in the uteroplacental circulation during preeclampsia. Whether the similar and reduced levels of iNOS mRNA expression in myometrium and placenta, respectively, in women with preeclampsia is of importance remains to be further evaluated.

The influence of recovery posture on post-exercise hypotension in normotensive men.

Postexercise hypotension may be the result of an impaired vasoconstrictor response. This hypothesis was investigated by examining the central and peripheral hemodynamic responses during supine and seated recovery after maximal upright exercise. After supine or seated baseline measurements, seven normotensive male volunteers completed a graded upright cycling protocol to volitional exhaustion. This was immediately followed by either supine or seated recovery. Measurements of pulsatile arterial blood pressure and central and peripheral hemodynamic variables recorded 30 min before exercise were compared with those taken throughout 60 min of recovery. Compared with baseline, mean arterial pressure (MAP) was reduced after exercise (P < 0.05) although the degree of change was not different between the supine (-9 +/- 4 mm Hg) and seated positions (-6 +/- 2 mm Hg). This change in MAP was associated with a reduction in diastolic blood pressure (DBP) (P < 0.05) and arterial pulse pressure (APP) (P < 0.01) for the supine and seated positions, respectively. The reduction in APP during seated recovery was accompanied by a decline in stroke volume (SV) (P < 0.05), not seen in the supine position, that limited the contribution of cardiac output (CO) to the maintenance of MAP. This effect of seated recovery was compensated by greater systemic (SVR) and regional vascular resistances in the forearm (FVR) and the forearm skin (SkVRA). There was also evidence of an augmented return of FVR and SkVRA to resting levels in the seated position after exercise. The lower peripheral resistance in the supine compared with seated recovery position suggests there is potential for greater vasoconstriction, although this is not evoked to increase blood pressure. This further suggests that the arterial baroreceptor reflex is reset to a lower operating pressure after exercise.

The angiotensin II AT1 receptor antagonist irbesartan prevents thromboxane A2-induced vasoconstriction in the rat hind-limb vascular bed in vivo.

We studied the vasoconstrictor effects of the thromboxane A2 (TxA2) analogue U46619 in the perfused hind limb of rats under constant flow before and after intravenous injection of irbesartan, an angiotensin II AT1 receptor antagonist, to test whether irbesartan interacts in vivo with the thromboxane A2/prostaglandin endoperoxidase H2 (TxA2/PGH2) receptor. Male Sprague-Dawley rats (n = 15, body weight 350-420 g) were anesthetized with thiobutabarbital sodium (Inactin, 100 mg/kg intraperitoneally). Regional vascular responses to U46619 (0.5 and 1.0 microg) were investigated in the rat hind quarter under conditions of controlled flow before and after administration of irbesartan (10 mg/kg, intravenously). In addition, to test the specificity of the effect of irbesartan on U46619, phenylephrine (0.5, 1.0 microg) and another AT1 receptor antagonist, candesartan CV11974 (0.3 mg/kg, intravenously) were used. The dose-dependent increases in hind-limb perfusion pressure produced by U46619 were significantly attenuated by prior injection of irbesartan, at a dose that blocked the angiotensin II (Ang II) pressor responses. The specificity for the response was shown with the demonstrations that the increase in vascular resistance produced by phenylephrine was unchanged by irbesartan and, furthermore, that the increase in vascular resistance produced by U46619 was unchanged by another AT1 receptor antagonist, candesartan. This study demonstrates that irbesartan interacts at the TxA2/PGH2 receptor in the rat's hind limb in vivo, to modify changes in local regional vascular resistance. The dual antagonistic actions of irbesartan, acting at both AT1 and TxA2 receptors in blood vessels, may overall enhance its therapeutic profile in the treatment of hypertension.

Changes in regional vascular resistance in response to microinjection of l-glutamate into different antero-posterior coordinates of the RVLM in awake rats

Changes in mean arterial pressure (MAP) and in regional vascular resistance (RVR, hindquarter, mesenteric and renal) induced by microinjection of l-glutamate into three different antero-posterior coordinates of the rostral ventrolateral medulla (RVLM) [1200–1600 μm ( n=10), 1601–2000 μm ( n=12) and 2001–2500 μm ( n=6) rostral to the obex] were investigated in unanesthetized rats. Guide cannulas directed towards the RVLM were implanted 4 days prior to the experiments. Doppler probes were implanted around the superior mesenteric, inferior abdominal aorta and left renal arteries and a catheter was inserted into the femoral artery and vein 1 day prior to the experiments. Insertion of the injector into the RVLM produced an increase in baseline MAP, which was back to control levels 2 min later, when l-glutamate was microinjected. Microinjection of l-glutamate (1 nmol/30 nl) into the three antero-posterior coordinates of the RVLM produced an increase in MAP associated with a similar increase in hindquarter, mesenteric and renal vascular resistance, which were back to control 1 min later. Saline into the RVLM produced negligible effects on MAP and RVR. These findings suggest that the sympathetic vasomotor neurons involved in the regulation of the regional vascular resistance in rats are not topographically distributed in the antero-posterior coordinates of the RVLM. However, the experimental methods used to evaluate the topographic distribution of sympatho-vasomotor neurons in the RVLM and the measurement of the regional blood flow may not be precise enough to detect any possible differences.

Role of nitric oxide in regional blood flow in angiotensin II-induced hypertensive rats.

The present study was designed to evaluate the contribution of nitric oxide (NO) to regional hemodynamics during the early phase of angiotensin II (Ang II)-induced hypertension. The responses of regional blood flow to chronic NO synthase inhibition with N(G)-nitro-L-arginine methyl ester (L-NAME) were assessed using radioactive microspheres in conscious Ang II-infused hypertensive rats. Ang II-infused rats (270 ng/kg/min, subcutaneously for 12 days: n=11) showed higher mean arterial pressure (MAP: 153+/-4 mmHg) and total peripheral resistance (TPR: 1.61+/-0.06 mmHg/min/ml), and lower cardiac output (CO: 102+/-3 ml/min) than vehicle-infused normotensive rats (115+/-2 mmHg, 0.96+/-0.05 mmHg/min/ml and 130+/-7 ml/min, n=11, respectively). The blood flow rates in the brain, spleen, large intestine and skin were significantly reduced in Ang III-infused rats compared with vehicle-infused rats, while those in the lung, heart, liver, kidney, adrenal gland, small intestine, and skeletal muscle were similar. Treating Ang II-infused rats with L-NAME (75 mg/l in drinking water for 10 days, n=11) resulted in higher MAP (166+/-6 mmHg) and TPR (1.89+/-0.18 mmHg/min/ml) and lower CO (87+/-7 m/min) than untreated Ang II-infused rats. L-NAME-treated Ang II-infused rats showed widespread increases in regional vascular resistance and reduced blood flow rates in the kidney (3.81+/-0.27 ml/min/g) and skeletal muscle (0.20+/-0.03 ml/min/g) compared with untreated Ang II-infused rats (6.88+/-0.27 and 0.33+/-0.04 ml/min/g, respectively). However, there were no significant differences in the flow rates of other organs investigated between these animals. An NO donor, (+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide (FK409: 30 microg/kg/min, i.v.), significantly decreased MAP (110+/-6 mmHg) and TPR (1.23+/-0.18 mmHg/min/ml) without significant changes in CO (89+/-9 ml/min) in L-NAME-treated Ang II-infused rats. Furthermore, FK409 partially reversed blood flow rates in the kidney (4.72+/-0.40 ml/min/g) and skeletal muscle (0.25+/-0.02 ml/min/g)in these animals. These results suggest that NO counteracts, at least in part, the vasoconstrictor effects of elevated Ang II levels in renal and skeletal muscle vascular beds, and is an important modulator in the regulation of blood flow to these organs during the development of Ang II-induced hypertension.

Systemic and Regional Hemodynamic Responses to Tempol in Angiotensin II-Infused Hypertensive Rats.

-Recent studies have indicated that angiotensin II (Ang II) can stimulate oxidative stress. The present study was conducted to assess the contribution of oxygen radicals to hypertension and regional circulation during Ang II-induced hypertension. With radioactive microspheres, the responses of systemic and regional hemodynamics to the membrane-permeable, metal-independent superoxide dismutase mimetic 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl (tempol) were assessed in conscious Ang II-infused hypertensive rats. Ang II-infused rats (80 ng/min SC for 12 days: n=25) showed higher mean arterial pressure (MAP: 161+/-4 mm Hg) and total peripheral resistance (TPR: 1.59+/-0.08 mm Hg. min(-1). mL(-1)) than vehicle-infused normotensive rats (116+/-3 mm Hg and 0.95+/-0.04 mm Hg. min(-1). mL(-1), respectively; n=23). The blood flow rates in the brain, spleen, large intestine, and skin were significantly reduced in Ang II-infused rats compared with vehicle-infused rats, whereas rates in the lung, heart, liver, kidney, stomach, small intestine, mesenterium, skeletal muscle, and testis were similar. Vascular resistance was significantly increased in every organ studied except the lung, in which the resistance was similar. Tempol (216 µmol/kg IV) significantly reduced MAP by 30+/-4% from 158+/-7 to 114+/-5 mm Hg and TPR by 35+/-6% from 1.57+/-0.17 to 0.95+/-0.04 mm Hg. min(-1). g(-1) in Ang II-infused rats (n=9) but had no effect on these parameters in vehicle-infused rats (n=8). In Ang II-infused rats, tempol did not affect regional blood flow but significantly decreased vascular resistance in the brain (29+/-6%), heart (31+/-6%), liver (37+/-7%), kidney (30+/-7%), small intestine (38+/-6%), and large intestine (47+/-7%). Ang II-infused hypertensive rats showed doubled vascular superoxide production (assessed with lucigenin chemiluminescence), which was normalized by treatment with tempol (3 mmol/L, n=7). Further studies showed that the NO synthase inhibitor, N:(omega)-nitro-L-arginine methyl ester (11 µmol. kg(-1). min(-1) IV, n=11) markedly attenuated the systemic and regional hemodynamic responses of tempol in Ang II-infused rats. These results suggest that in this model of hypertension, oxidative stress may have contributed to the alterations in systemic blood pressure and regional vascular resistance through inactivation of NO.

Central versus peripheral mediation of naloxone's perfusion effects in endotoxic rats.

Opioid receptor antagonists can act centrally and peripherally. It is unclear if these 2 pathways differentially mediate the perfusion-associated effects of opioid antagonism during endotoxemia. Male, Sprague-Dawley rats (340-390 g) were surgically prepared with left ventricular, tail artery, and jugular vein catheters 24 h before experiments were begun. Conscious, unrestrained rats were challenged with Escherichia coli lipopolysaccharide (LPS; 2 mg/kg/hr over 30 min) infusion. Measurements of regional blood flows were made using radioactive microspheres prior to (baseline), and at 60 and 120 min after LPS infusion. Saline (1 mL/kg bolus + 0.5 mL/kg/h infusion), naloxone (Nlx; 4 mg/kg bolus + 2 mg/kg/h infusion), or naloxone methyl bromide (Nlx-mb; 4.64 mg/kg, bolus + 2.32 mg/kg/h infusion) were administered 40 min after LPS infusion was begun. Nlx-mb does not cross the blood-brain barrier, and was thus used to differentiate central from peripherally mediated responses. At the end of each experiment, blood samples were collected for determination of ET-1 and nitric oxide metabolites (NOx = NO3 + NO2) using enzyme-linked immunosorbent assay (ELISA) and Griess reaction methods, respectively. Endotoxemia produced a significant decrease in cardiac output and an increase in systemic vascular resistance. Treatment with Nlx or Nlx-mb significantly attenuated the endotoxin-induced elevation in systemic vascular resistance and the decrease in cardiac output at 60 min after induction of endotoxemia compared with their respective baseline values. Nlx and Nlx-mb also attenuated the endotoxin-induced increases in hepatic portal and skeletal vascular resistances. These observations suggested that the ameliorative effect of Nlx on endotoxemia-induced regional vascular resistance alterations was mediated via peripheral opioid receptor mechanisms. However, although Nlx attenuated the endotoxin-induced decreases in the blood flow to the stomach and pancreas, Nlx-mb attenuated the endotoxin-induced decreases in the blood flow to the small intestine and cecum, in addition to the pancreas and, to some extent, the stomach. As such, separate central and peripherally mediated actions of opioid receptor antagonism were indicated. Nlx also resulted in an increase in the plasma levels of ET-1 only, whereas Nlx-mb increased the plasma levels of ET-1 and NOx. These observations suggest that separate central and peripheral effects of opioids during endotoxemia play a role in the associated circulatory alterations, and may differentially affect the release and/or synthesis of vasoactive mediators that might be related to their varied hepatosplanchnic vascular response during endotoxemia.

Regional hemodynamics after chronic nitric oxide inhibition in spontaneously hypertensive rats.

Inhibition of nitric oxide (NO) synthase by L-arginine analogs is associated with elevation of blood pressure in rats. Because endothelium-dependent vasomotion in different vascular beds is not homogenous, the aim of this study was to characterize and compare regional hemodynamic responses in carotid, femoral, and renal vascular beds after chronic NO inhibition in spontaneously hypertensive rats. The possible role of circulating endothelin and renin angiotensin systems in mediating the effects of chronic NO inhibition was also studied. Systemic and regional hemodynamics, left ventricular mass, plasma renin activity, and plasma endothelin-1 were determined in control and Nomega-nitro-Larginine methyl ester (L-NAME)-treated (10 mg/kg/day, 4 weeks) spontaneously hypertensive rats. L-NAME treatment increased arterial pressure and total peripheral and regional vascular resistance and decreased cardiac output, stroke volume, and regional blood flow. An increase in blood flow ratio and a decrease in vascular resistance ratio between carotid and renal as well as femoral and renal vascular beds in rats treated with L-NAME was found. Blood flow and vascular resistance ratios between femoral and carotid vascular beds remained unchanged. L-NAME increased plasma renin activity and left ventricular weight/body weight ratio, whereas plasma endothelin-1 was not modified. The results of this study showed that the renal circulation seemed to be more sensitive to the effects of chronic NO inhibition than carotid and femoral vascular beds. Simultaneous activation of the renin angiotensin system may further potentiate cardiovascular effects of chronic NO inhibition. No evidence that circulating endothelin-1 plays a role in this model of hypertension was found.

Changes in regional vascular resistance in response to microinjection of l-glutamate into different antero-posterior coordinates of the RVLM in awake rats

Changes in mean arterial pressure (MAP) and in regional vascular resistance (RVR, hindquarter, mesenteric and renal) induced by microinjection of l-glutamate into three different antero-posterior coordinates of the rostral ventrolateral medulla (RVLM) [1200–1600 μm ( n=10), 1601–2000 μm ( n=12) and 2001–2500 μm ( n=6) rostral to the obex] were investigated in unanesthetized rats. Guide cannulas directed towards the RVLM were implanted 4 days prior to the experiments. Doppler probes were implanted around the superior mesenteric, inferior abdominal aorta and left renal arteries and a catheter was inserted into the femoral artery and vein 1 day prior to the experiments. Insertion of the injector into the RVLM produced an increase in baseline MAP, which was back to control levels 2 min later, when l-glutamate was microinjected. Microinjection of l-glutamate (1 nmol/30 nl) into the three antero-posterior coordinates of the RVLM produced an increase in MAP associated with a similar increase in hindquarter, mesenteric and renal vascular resistance, which were back to control 1 min later. Saline into the RVLM produced negligible effects on MAP and RVR. These findings suggest that the sympathetic vasomotor neurons involved in the regulation of the regional vascular resistance in rats are not topographically distributed in the antero-posterior coordinates of the RVLM. However, the experimental methods used to evaluate the topographic distribution of sympatho-vasomotor neurons in the RVLM and the measurement of the regional blood flow may not be precise enough to detect any possible differences.

Reduced muscle vascular resistance in intrauterine growth restricted newborn piglets

It has been shown that asymmetrical intrauterine growth restriction is denoted by disproportional reduction of muscle mass compared to body weight reduction. However, the effects of IUGR on regional vascular resistance and blood flow of skeletal muscles and their contractile function have not been studied until now. Therefore, muscle blood flow (MBF) and isometric force output of serial stimulated hindlimb plantar flexors was measured in thiopental -anesthetized normal weight (NW; n = 9) and intrauterine growth restricted (IUGR; n = 9) one-day-old piglets. Additionally, muscle vascular resistance (MVR) and thyroid hormones were estimated. MBF was found to be markedly increased in IUGR piglets by 36% with a concomitant MVR reduction of 37% (p < 0.05). Isometric force of the plantar flexors was considerably higher in NW than in IUGR piglets (p < 0.05). However, amount of muscle fatigue was more pronounced in NW piglets (9.1+/-2.8%) than was in IUGR piglets (3.7+/-2.3%) (p < 0.05). Furthermore, specific tension of NW muscles (18.8+/-0.7 N/cm2) was significantly lower than for IUGR muscles (21.2+/-0.9 N/cm2) (P<0.05). IUGR newborn piglets exhibited increased plasma levels of thyroxine (T4) (p < 0.05), whereas triiodothyronine (T3) showed similar values in both animal groups. These data clearly indicate that muscle hemodynamics and contractile function are more developed in newborn IUGR piglets. Furthermore it is suggested that the improved tolerance to fatigue during isometric contractions may indicate an increased oxidative capacity of calf muscles due to intrauterine growth restriction.

Adenosine and nitric oxide regulate regional vascular resistance via interdependent and independent mechanisms during sepsis.

Adenosine receptor blockade increases regional resting vascular resistance during sepsis. In healthy subjects, part of adenosine's actions are mediated via stimulation of nitric oxide synthase. Because nitric oxide synthase activity is thought to be a major contributor to altered vascular tone in sepsis, we tested the hypothesis that some of the nitric oxide-mediated resting regional resistance during sepsis is secondary to endogenous adenosine stimulation of nitric oxide synthase. Prospective, randomized, controlled experiment. Shock-trauma and basic science laboratory. Male Sprague-Dawley rats. Twenty-four hours after sepsis or sham induction, rats were separated into two groups (n = 6 to 10 in each group). Group 1 received a 10-min infusion of the adenosine antagonist 8-sulfophenyltheophylline (0.9 mg/kg x min) followed by a 10-min infusion of L-nitro-arginine-methyl ester (0.5 mg/kg x min). Group 2 similarly received L-nitro-arginine-methyl ester followed by 8-sulfophenyltheophylline in the presence of L-nitro-arginine-methyl ester. Hemodynamic and blood flow measurements (microspheres) were made before infusions, 10 mins after the administration of each single-agent infusion, and 10 mins after combined-agent infusions were administered. No significant resistance alterations were observed in nonseptic rats. In septic rats, adenosine receptor blockade alone increased hepatosplanchnic and skeletal muscle vascular resistance, but no further increases were seen when L-nitro-arginine-methyl ester was added. Nitric oxide synthase inhibition alone increased hepatosplanchnic and skeletal muscle vascular resistances. When 8-sulfophenyltheophylline was added to the infusion, skeletal muscle vascular resistance increased significantly more than with L-nitro-arginine-methyl ester alone, but there were no further increases in hepatosplanchnic resistance. Renal and adipose vascular resistances increased with L-nitro-arginine-methyl ester infusions, and 8-sulfophenyltheophylline produced no effect. During sepsis, nitric oxide caused resting vasodilation independent of adenosine in the renal and adipose vasculature. In the hepatosplanchnic circulation, there is reciprocal adenosine-nitric oxide interaction in maintaining resting regional resistance. Skeletal muscle displayed a dual adenosine-mediated (nitric oxide-independent) and nitric oxide-mediated (adenosine receptors required) interaction to regulate resting resistance during sepsis. These data indicate that in the hepatosplanchnic and skeletal muscle vasculature, all of the resting nitric oxide-mediated vasodilation is secondary to endogenous adenosine action, but in adipose and renal vasculature, resting nitric oxide mediated vasodilation is independent of adenosine. Endogenous adenosine also appears to play a significant role in determining resting skeletal muscle resistance that is independent of nitric oxide synthase during sepsis.

Effect of Distension of the Gallbladder on Plasma Renin Activity in Anesthetized Pigs

Gallbladder pathology has been associated with cardiovascular disease. Recently, we showed that gallbladder distension in anesthetized pigs reflexly increased heart rate, arterial pressure, and coronary and renal vascular resistance through efferent sympathetic mechanisms. Renin release is affected by sympathetic output, and angiotensin liberation may result in vasoconstriction. This study was undertaken to determine whether gallbladder distension primarily causes a reflex change in plasma renin activity (PRA) and to assess its influence on observed pressor and coronary responses as well as on regional vascular resistance. In 34 alpha-chloralose-anesthetized pigs, balloons positioned within the gallbladder were distended for 30 minutes with volumes of Ringer's solution equal to those of withdrawn bile. In 19 pigs, gallbladder distension at constant heart rate, arterial pressure, and renal flow increased PRA in the absence of changes in urinary sodium excretion. This increase was abolished by cervical vagotomy, section of renal nerves, or blockade of beta-adrenergic receptors. In another 15 pigs, blockade of angiotensin II receptors significantly attenuated the pressor and coronary, mesenteric, and iliac vasoconstriction responses to gallbladder distension. The present study showed that innocuous gallbladder distension primarily caused a reflex increase in PRA. This increase, which involved afferent vagal pathways and efferent sympathetic mechanisms related to beta-adrenergic receptors, contributed significantly to the pressor and coronary, mesenteric, and iliac vasoconstriction responses to gallbladder distension.

Effects of N-methyl- L-arginine on cardiac and regional blood flow in a dog endotoxin shock model

Purpose: Indirect evidence suggests a decrease in organ perfusion as a result of nitric oxide (NO) inhibition in endotoxic shock. Cardiac and regional hemodynamic responses to N-methyl- L-arginine (L-NMA), a nonspecific inhibitor of constitutive and inducible nitric oxide synthase (NOS), were assessed in nine conscious dogs subjected to endotoxin. Materials and Methods: Lipopolysaccharide (LPS) was titrated to a maximum of 200 μg/kg, IV, over 45 minutes. L-NMA was given in a dose of 20 mg/kg, IV. Hemodynamic parameters were recorded for 6 hours following L-NMA administration. Results: LPS induced significant decreases in mean arterial blood pressure (MAP), cardiac output (CO), first derivative of left ventricular pressure (dP/dt), coronary blood flow, carotid blood flow, mesenteric blood flow, renal blood flow, and a significant hepatic vasodilation. L-NMA fully reversed the effects of LPS on MAP, heart rate, dP/dt, coronary and carotid blood flow, and reversed mesenteric blood flow and hepatic blood flow at 1 and 3 hours, respectively. L-NMA partially overcame the LPS-induced decrease in renal blood flow at 30 minutes and 1 hour. Except for mesenteric and carotid circulation, L-NMA did not change regional vascular resistance. Conclusions: It is likely that constitutive NOS is implicated in immediate cardiac, carotid, mesenteric, and renal vascular changes, whereas inducible NOS accounted for delayed responses in hepatic and coronary circulation. Copyright © 2000 by W.B. Saunders Company

In vivo evidence that l- S-nitrosocysteine may exert its vasodilator effects by interaction with thiol residues in the vasculature

This study examined the effects of the lipophobic thiol chelator, para-hydroxymercurobenzoic acid (25 and 50 μmol/kg, i.v.) on the falls in mean arterial blood pressure and regional vascular resistances produced by l- S-nitrosocysteine (400 nmol/kg, i.v.) and the nitric oxide (NO)-donors, ( Z)-1-| N-methyl- N-[6( N-methylammoniohexyl)amino]|diazen-1-ium-1,2-diolate (MAHMA NONOate, 25 nmol/kg, i.v.) and sodium nitroprusside (10 μg/kg, i.v.), in urethane-anesthetized rats. The l- S-nitrosocysteine-induced responses were markedly diminished whereas the MAHMA NONOate- and sodium nitroprusside-induced responses were minimally affected by para-hydroxymercurobenzoic acid. These results suggest that the vasodilator actions of l- S-nitrosocysteine involves the interaction with membrane thiols in vascular smooth muscle of resistance arteries and that para-hydroxymercurobenzoic acid does not markedly affect NO-mediated vasodilation.

I: Haemodynamics, regulation of vascular resistance, hypertension (basic)

I: Haemodynamics, regulation of vascular resistance, hypertension (basic)

Brain Atrial Natriuretic Peptide Family Abolishes Cardiovascular Haemodynamic Alterations Caused By Hypertonic Saline In Rats

1. Regional haemodynamic alterations caused by hypertonic NaCl solution (Hi-Salt; 10%, 10 microL) injected intracerebroventricularly (i.c.v.) were investigated by using radioactive microspheres in anaesthetized rats. 2. Intracerebroventricular injections of Hi-Salt increased regional vascular resistance of visceral organs, including the kidney, and elevated plasma levels of vasopressin. 3. Intracerebroventricular pretreatment with TCV-11974 (50 micrograms/10 microL/nat), an angiotensin AT1 receptor antagonist, attenuated the pressor response and vasopressin release to subsequently injected Hi-Salt, but did not affect regional haemodynamic effects of i.c.v. Hi-Salt on vascular resistance. 4. In contrast, i.c.v. pretreatment with atrial natriuretic polypeptide (ANP) or type-C natriuretic polypeptide (CNP) almost completely abolished the haemodynamic changes and vasopressin release caused by i.c.v. Hi-Salt. 5. The present findings indicate that a natriuretic family in the brain may be involved to a great degree in the central regulation of salt-induced hypertension in rats, while brain angiotensin II is likely to participate only in vasopressin release.

Effects of intravenous administration of prostacyclin on regional blood circulation in awake rats.

1. The effects of intravenous infusion of prostacyclin (PGI2, 0.1, 0.2, 0.3 and 1.0 microg kg(-1) min(-1) lasting 5 min) on regional blood flow and regional vascular resistance have been studied in awake rats using the radioactive microsphere method. 2. The control values of blood flow to the heart, kidney, small intestine, hind limb muscle, pericranial skin and brain as well as the corresponding vascular resistance were not modified by an i.v. infusion (0.1 ml min(-1)) of Tris-buffer (the vehicle of PGI2). 3. The i.v. infusion of PGI2 produced graded dose-dependent decreases of MAP (r=0.87, P<0.001; ED20=0.73 [0.13-2.55] microg kg(-1) min(-1)) as well as decreases of vascular resistance in the heart (r=0.83, P<0.001; ED30=0.17 [0.09-0.31] microg kg(-1) min(-1)), pericranial skin (r=0.88, P<0.001; ED30=0.28 [0.18-0.43] microg kg(-1) min(-1)) and small intestine (r=0.74, P<0.001; ED30=0.21 [0.11-0.39] microg kg(-1) min(-1)), which led to dose-related increases of blood flow to these territories. 4. On the contrary, PGI2 increased vascular resistance in skeletal muscle (r=0.73, P<0.001; ED30=0.20 [0.10-0.39] microg kg(-1) min(-1)) with corresponding reductions in blood flow. The low doses reduced renal blood flow but there were no significant changes during the high ones. Cerebral vessels did not dilate during any infusion of PGI2 and cerebral blood flow decreased as MAP fell (r=0.56, P<0.01). 5. We conclude that, in awake rats, the coronary vessels are extremely sensitive to the vasodilating effect of PGI2 and that the mesenteric vessels and those of the pericranial skin are very responsive too. Moreover, autoregulation is inefficient to maintain cerebral blood flow during infusion of PGI2.

Regulation of autonomic pathways by angiotensin

Angiotensin II (ANG) is an 8 amino acid peptide recognized for its endocrine roles in the regulation of vascular resistance and aldosterone secretion. In addition to theses roles it is now well established that ANG exerts significant control over the autonomic nervous system as a result of specific

Regional hemodynamic responses to exogenous catecholamines and vasoactive peptides in conscious rats.

The vasoactive hormones vasopressin, angiotensin II, adrenaline, and noradrenaline may all be released after central neural stimulation, but our knowledge of their relative actions on regional vascular resistances is incomplete. A comprehensive account of these patterns will help our understanding of their contributions to centrally generated patterns of blood flow. In the present study, regional blood flows and resistances of five major arteries were measured during sequential intravenous infusions of a range of doses of each substance in conscious rats. Vasopressin strongly increased superior mesenteric, hindquarters, carotid, and renal resistance but did not affect celiac artery resistance until the highest infusion rate. Both angiotensin II and noradrenaline increased resistance, although to different extents, in all vascular beds except the hindquarters, which was unaffected. Adrenaline infused at pressor rates markedly increased superior mesenteric resistance while moderately increasing renal, carotid and celiac arterial resistances. At subpressor rates, however, adrenaline increased celiac resistance but decreased hindquarters vascular resistance without significantly affecting the other beds. It is concluded that each vasoactive substance released into the systemic circulation causes its own characteristic pattern of vascular responses. This information should be useful for understanding the humoral basis of hemodynamic responses to central stimuli.