Efficacy of nifedipine to prevent systemic and renal vasoconstrictor effects of endothelin

1990 ◽  
Vol 259 (2) ◽  
pp. F304-F311 ◽  
Author(s):  
P. Madeddu ◽  
X. P. Yang ◽  
V. Anania ◽  
C. Troffa ◽  
A. Pazzola ◽  
...  
Keyword(s):  
Bolus Injection ◽  
Regression Line ◽  
The Other ◽  
Base Line ◽  
Intravenous Bolus ◽  
Ang Ii ◽  
Hemodynamic Parameters ◽  
Renal Vasoconstriction ◽  
Induced Changes ◽  
The Relationship

We investigated whether systemic and renal vasoconstriction induced by porcine endothelin (endothelin 1) is prevented by nifedipine in awake normotensive rats. Endothelin (0.07-1.4 nmol/kg iv) induced a long-lasting increase in mean blood pressure (MBP) and a decrease in renal blood flow (RBF). Maximal decrease in RBF was 25 +/- 7% (0.07 nmol/kg), 40 +/- 2 (0.35), 67 +/- 5 (0.70), and 74 +/- 8 (1.4). Hemodynamic parameters were back to base line within 35 +/- 5 min (0.07 nmol/kg), 43 +/- 6 (0.35), 60 +/- 4 (0.70), and 81 +/- 7 (1.4). Intravenous bolus injection of either angiotensin II (ANG II, 0.006-0.024 nmol/kg) or norepinephrine (0.40-1.60 nmol/kg) caused a dose-related short-lasting increase in MBP and a decrease in RBF. Endothelin was less potent than ANG II (1:3.42) and more potent than norepinephrine (1:0.015) as a renal vasoconstrictor. Nifedipine (1 mg/kg ip) was equally effective in preventing the increase in MBP caused by endothelin, norepinephrine, or ANG II. It exerted a weaker protection on the renal hemodynamic response to endothelin compared with the inhibition of the other two vasoconstrictors. Thus the regression line representing the relationship between endothelin-induced changes in MBP and RBF was steeper in rats given nifedipine (slope: vehicle, -1.33; nifedipine, -5.50; P less than 0.05). These studies suggest that nifedipine can partially prevent systemic and renal vasoconstriction caused by exogenously administered endothelin in awake normotensive rats.

Cerebral hypoperfusion modifies the respiratory chemoreflex during orthostatic stress

2013 ◽  
Vol 125 (1) ◽  
pp. 37-44 ◽  
Author(s):  
Shigehiko Ogoh ◽  
Hidehiro Nakahara ◽  
Kazunobu Okazaki ◽  
Damian M. Bailey ◽  
Tadayoshi Miyamoto
Keyword(s):  
Lower Body Negative Pressure ◽  
Minute Ventilation ◽  
Regression Line ◽  
Cerebral Hypoperfusion ◽  
Orthostatic Stress ◽  
Respiratory Chemoreflex ◽  
Underlying Mechanisms ◽  
End Tidal ◽  
Induced Changes ◽  
The Relationship

The respiratory chemoreflex is known to be modified during orthostatic stress although the underlying mechanisms remain to be established. To determine the potential role of cerebral hypoperfusion, we examined the relationship between changes in MCA Vmean (middle cerebral artery mean blood velocity) and V̇E (pulmonary minute ventilation) from supine control to LBNP (lower body negative pressure; −45mmHg) at different CO2 levels (0, 3.5 and 5% CO2). The regression line of the linear relationship between V̇E and PETCO2 (end-tidal CO2) shifted leftwards during orthostatic stress without any change in sensitivity (1.36±0.27 l/min per mmHg at supine to 1.06±0.21 l/min per mmHg during LBNP; P=0.087). In contrast, the relationship between MCA Vmean and PETCO2 was not shifted by LBNP-induced changes in PETCO2. However, changes in V̇E from rest to LBNP were more related to changes in MCA Vmean than changes in PETCO2. These findings demonstrate for the first time that postural reductions in CBF (cerebral blood flow) modified the central respiratory chemoreflex by moving its operating point. An orthostatically induced decrease in CBF probably attenuated the ‘washout’ of CO2 from the brain causing hyperpnoea following activation of the central chemoreflex.

Vasoconstrictor-induced changes in renal blood flow: role of prostaglandins and histamine

1988 ◽  
Vol 254 (4) ◽  
pp. F470-F476 ◽  
Author(s):  
R. O. Banks
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Histidine Decarboxylase ◽  
Reactive Hyperemia ◽  
Constant Infusion ◽  
Base Line ◽  
Ang Ii ◽  
Renal Vasoconstriction ◽  
Control Value

The role of histamine (H) and prostaglandins (PGs) in the renal vasoconstriction prompted by a 10-min intrarenal infusion of norepinephrine (NE, 0.2 micrograms), antidiuretic hormone (ADH, 10 mU), or angiotensin II (ANG II, 0.05 micrograms) was evaluated in anesthetized dogs (amounts are per min per kg). Renal blood flow (RBF, flow probe) decreased four- to fivefold during the 1st min of infusion with each agonist but then gradually returned toward base line. This “escape” was greatest with ADH, less with NE, and small with ANG II. There was a postinfusion reactive hyperemia (RH) only after NE; NE-RH was 4.26 +/- 0.75 (SE) ml/g. Meclofenamate (MFA) reduced NE-RH to 60 +/- 11% of control and decreased NE escape. The H1-receptor antagonist, chlorpheniramine (CP), decreased NE-RH to 24 +/- 5% of control and reduced NE escape. MFA slowed, but did not block, ADH escape and had little effect on ANG II escape. CP did not affect ADH or ANG II escape. The histidine decarboxylase inhibitor, p-toluenesulfonohydrazine, did not affect NE escape but decreased NE-RH to 22 +/- 6% of control. Bolus injections of ADH during a constant infusion of the hormone were not vasoactive, indicating a tachyphylaxis-like phenomenon; this was not found with ANG II or NE. Finally, the excretion of histamine-like material increased from a control value of 0.69 +/- 0.08 to 1.28 +/- 0.28 micrograms/min during NE-RH. These results indicate that NE releases histamine and PGs from the kidney and that PGs account, primarily, for NE escape, whereas histamine accounts, primarily, for NE-RH.

Contribution of central ANG II to acute stress-induced changes in baroreflex function in young rats

2000 ◽  
Vol 279 (4) ◽  
pp. R1386-R1391 ◽  
Author(s):  
James P. Porter
Keyword(s):  
Receptor Antagonist ◽  
Acute Stress ◽  
Central Action ◽  
Ang Ii ◽  
Maternal Influences ◽  
Baroreflex Function ◽  
Old Rats ◽  
Freely Moving ◽  
Induced Changes ◽  
The Relationship

The aim of the present investigation was to characterize the baroreflex in weaned 23- to 25-day-old rats when maternal influences were no longer present. The relationship between mean arterial pressure (MAP) and heart rate (HR) was determined during baroreceptor loading with phenylephrine and baroreceptor unloading with sodium nitroprusside in conscious rats, first in the freely moving state and subsequently during acute stress. In unstressed rats, the slope of the relationship between MAP and HR was greater during baroreceptor loading than baroreceptor unloading. Acute stress significantly attenuated the slope of the response to baroreceptor loading but increased the slope of the response to baroreceptor unloading. Pretreatment with intracerebroventricular or intravenous losartan, an AT1 receptor antagonist, or intracerebroventricular α-helical corticotropin-releasing hormone (α-hCRH), a receptor antagonist, before the stress significantly reduced the stress-induced attenuation of slope during baroreceptor loading. Hence, young postweaning rats can alter baroreflex function during acute stress in a manner that would favor increases in MAP. Even at this young age, a central action of ANG II and CRH contributes to these stress-induced adaptations.

Abstract 493: Impact of Renal Vasoconstriction on the Relationship Between Blood Pressure and Renal Injury in Angiotensin II-induced Hypertensive Rats

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Aaron J Polichnowski ◽  
Maria Picken ◽  
Jianrui Long ◽  
Geoffrey Williamson ◽  
Karen Griffin ◽  
...  
Keyword(s):  
Renal Injury ◽  
Left Kidney ◽  
Separate Experiment ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Osmotic Minipump ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
Induced Hypertension ◽  
The Relationship

Ang II is thought to play a prominent role in the development of hypertension-induced renal disease via BP dependent and independent pathways; however the quantitative relationships between BP and renal injury have not been rigorously examined in Ang II-induced hypertension. The major goals of the present study were to assess: 1) the relationship between BP and renal injury in rats with hypertension induced by Ang II vs. renal mass reduction (RMR) and 2) the pressure-flow relationships in conscious Ang II-infused rats. One group of male Sprague-Dawley rats (Charles River) were implanted with a BP radiotransmitter and 10 days later administered Ang II (n=12; 500 ng/kg/min via osmotic minipump) or subjected to 3/4 RMR via right uninephrectomy + infarction of ∼ 1/2 of the left kidney (RKI, n=5). BP was measured continuously and kidneys were perfused fixed at 6 weeks for the assessment of renal injury. In a separate experiment, MAP and RBF (Transonic) were measured in conscious chronically instrumented rats. After recovery from surgery (∼7 days), baseline MAP and RBF were assessed (∼4 hours @ 200 Hz) on 2 consecutive days. Subsequently, rats were administered Ang II (n=6; 500 ng/kg/min) or saline (n=7; sham) via osmotic minipump and MAP and RBF were again assessed every 2-3 days for 10 days. Despite a higher average systolic BP over 6 weeks in Ang II (174±3 mmHg) vs. RKI (165±6 mmHg) rats, glomerulosclerosis (GS) was higher (p<0.05) in RKI (15±7% out of 100 glomeruli) vs. Ang II (6±1% out of 100 glomeruli) rats. Moreover, the slope of the relationship between BP and %GS (Δ%GS/ΔmmHg) was greater in RKI vs. Ang II rats. Both MAP (98±2 vs. 99±3 mmHg) and RBF (8.1±1vs. 8.2±1 ml/min) were similar at baseline in Ang II and sham rats, respectively. MAP was elevated by day 3 (123±6 mmHg) and further increased to 157±5 mmHg by day 10 in Ang II rats. Conversely, RBF was decreased at day 3 (6.6±0.6 ml/min) and the vasoconstriction persisted over the experimental protocol as RBF further decreased to 5.6±0.7 ml/min at day 10 in Ang II rats. In conclusion, Ang II-induced hypertension is associated with a diminished susceptibility to renal injury as compared to rats with RMR likely due, in part, to the AngII-induced vasoconstriction, which reduces BP transmission to the renal microvasculature.

scholarly journals Hemodynamic basis for the limited renal injury in rats with angiotensin II-induced hypertension

2015 ◽  
Vol 308 (3) ◽  
pp. F252-F260 ◽  
Author(s):  
Aaron J. Polichnowski ◽  
Karen A. Griffin ◽  
Maria M. Picken ◽  
Hector Licea-Vargas ◽  
Jianrui Long ◽  
...  
Keyword(s):  
Chronic Administration ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Glomerular Injury ◽  
Tubulointerstitial Injury ◽  
Injury Score ◽  
Renal Vasoconstriction ◽  
Sprague Dawley Rats ◽  
The Relationship ◽  
Pharmacological Model

ANG II is thought to increase the susceptibility to hypertension-induced renal disease (HIRD) via blood pressure (BP)-dependent and BP-independent pathways; however, the quantitative relationships between BP and HIRD have not been examined in ANG II-infused hypertensive rats. We compared the relationship between radiotelemetrically measured BP and HIRD in Sprague-Dawley rats (Harlan) chronically administered ANG II (300–500 ng·kg−1·min−1, n = 19) for 4 wk versus another commonly employed pharmacological model of hypertension induced by the chronic administration of Nω-nitro-l-arginine methyl ester (l-NAME, 50 mg·kg−1·min−1, n = 23). Despite the significantly higher average systolic BP associated with ANG II (191.1 ± 3.2 mmHg) versus l-NAME (179.9 ± 2.5 mmHg) administration, the level of HIRD was very modest in the ANG II versus l-NAME model as evidenced by significantly less glomerular injury (6.6 ± 1.3% vs. 11.3 ± 1.5%, respectively), tubulointerstitial injury (0.3 ± 0.1 vs. 0.7 ± 0.1 injury score, respectively), proteinuria (66.3 ± 10.0 vs. 117.5 ± 10.1 mg/day, respectively), and serum creatinine levels (0.5 ± 0.04 vs. 0.9 ± 0.07 mg/dl, respectively). Given that HIRD severity is expected to be a function of renal microvascular BP transmission, BP-renal blood flow (RBF) relationships were examined in additional conscious rats administered ANG II ( n = 7) or l-NAME ( n = 8). Greater renal vasoconstriction was observed during ANG II versus l-NAME administration (41% vs. 23% decrease in RBF from baseline). Moreover, administration of ANG II, but not l-NAME, led to a unique BP-RBF pattern in which the most substantial decreases in RBF were observed during spontaneous increases in BP. We conclude that the hemodynamic effects of ANG II may mediate the strikingly low susceptibility to HIRD in the ANG II-infused model of hypertension in rats.

The Relationship Between Suicidal Thinking and Dating Violence in a Sample of Adolescent Abortion Patients

Crisis ◽  
2011 ◽  
Vol 32 (5) ◽  
pp. 246-253 ◽  
Author(s):  
Gretchen E. Ely ◽  
William R. Nugent ◽  
Julie Cerel ◽  
Mholi Vimbba
Keyword(s):  
Unintended Pregnancy ◽  
Dating Violence ◽  
Young Women ◽  
Psychosocial Problems ◽  
The Other ◽  
Assessment Scale ◽  
Adolescent Dating Violence ◽  
Adolescent Relationships ◽  
Suicidal Thinking ◽  
The Relationship

Background: The relationship between suicidal thinking and adolescent dating violence has not been previously explored in a sample of adolescent abortion patients. Aims: This paper highlights a study where the relationship between dating violence and severity of suicidal thinking was examined in a sample of 120 young women ages 14–21 seeking to terminate an unintended pregnancy. Methods: The Multidimensional Adolescent Assessment Scale and the Conflict in Adolescent Relationships Scale was used to gather information about psychosocial problems and dating violence so that the relationship between the two problems could be examined, while controlling for the other psychosocial problems. Results: The results suggest that dating violence was related to severity of suicidal thinking, and that the magnitude of this relationship was moderated by the severity of problems with aggression. Conclusions: Specifically, as the severity of participant’s general problems with aggression increased, the magnitude of the relationship between dating violence and severity of suicidal thinking increased. Limitations of the study and implications for practice are discussed.

Emotional Impact Feedback Changes How We Remember Negative Autobiographical Experiences

2010 ◽  
Vol 57 (5) ◽  
pp. 354-359 ◽  
Author(s):  
Melanie K. T. Takarangi ◽  
Deryn Strange
Keyword(s):  
Well Being ◽  
The Other ◽  
Personal Perspective ◽  
Emotional Impact ◽  
Potential Mechanism ◽  
Negative Experiences ◽  
Negative Memory ◽  
The Relationship ◽  
Negative Memories ◽  
Over Time

When people are told that their negative memories are worse than other people’s, do they later remember those events differently? We asked participants to recall a recent negative memory then, 24 h later, we gave some participants feedback about the emotional impact of their event – stating it was more or less negative compared to other people’s experiences. One week later, participants recalled the event again. We predicted that if feedback affected how participants remembered their negative experiences, their ratings of the memory’s characteristics should change over time. That is, when participants are told that their negative event is extremely negative, their memories should be more vivid, recollected strongly, and remembered from a personal perspective, compared to participants in the other conditions. Our results provide support for this hypothesis. We suggest that external feedback might be a potential mechanism in the relationship between negative memories and psychological well-being.

Haematocrit: Relationships with Blood Lipids, Blood Pressure and other Cardiovascular Risk Factors

1994 ◽  
Vol 72 (01) ◽  
pp. 058-064 ◽  
Author(s):  
Goya Wannamethee ◽  
A Gerald Shaper
Keyword(s):  
Physical Activity ◽  
Risk Factors ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Cardiovascular Risk ◽  
Cardiovascular Risk Factors ◽  
Alcohol Intake ◽  
Blood Lipids ◽  
The Other ◽  
The Relationship

SummaryThe relationship between haematocrit and cardiovascular risk factors, particularly blood pressure and blood lipids, has been examined in detail in a large prospective study of 7735 middle-aged men drawn from general practices in 24 British towns. The analyses are restricted to the 5494 men free of any evidence of ischaemic heart disease at screening.Smoking, body mass index, physical activity, alcohol intake and lung function (FEV1) were factors strongly associated with haematocrit levels independent of each other. Age showed a significant but small independent association with haematocrit. Non-manual workers had slightly higher haematocrit levels than manual workers; this difference increased considerably and became significant after adjustment for the other risk factors. Diabetics showed significantly lower levels of haematocrit than non-diabetics. In the univariate analysis, haematocrit was significantly associated with total serum protein (r = 0*18), cholesterol (r = 0.16), triglyceride (r = 0.15), diastolic blood pressure (r = 0.17) and heart rate (r = 0.14); all at p <0.0001. A weaker but significant association was seen with systolic blood pressure (r = 0.09, p <0.001). These relationships remained significant even after adjustment for age, smoking, body mass index, physical activity, alcohol intake, lung function, presence of diabetes, social class and for each of the other biological variables; the relationship with systolic blood pressure was considerably weakened. No association was seen with blood glucose and HDL-cholesterol. This study has shown significant associations between several lifestyle characteristics and the haematocrit and supports the findings of a significant relationship between the haematocrit and blood lipids and blood pressure. It emphasises the role of the haematocrit in assessing the risk of ischaemic heart disease and stroke in individuals, and the need to take haematocrit levels into account in determining the importance of other cardiovascular risk factors.

A Novel Chimaeric Derivative of Saruplase, rscu-PA-40kDA/Hir, Binds to Thrombin and Exerts Thrombus-specific Fibrinolysis in Arterial and Venous Thrombosis in Dogs

1997 ◽  
Vol 77 (03) ◽  
pp. 535-539 ◽  
Author(s):  
J Schneider ◽  
R Hauser ◽  
H-H Hennies ◽  
J Korioth ◽  
G Steffens ◽  
...  
Keyword(s):  
Venous Thrombosis ◽  
Plasma Levels ◽  
Time Course ◽  
Bolus Injection ◽  
Specific Activity ◽  
Intravenous Bolus ◽  
Protease Domain ◽  
Parent Molecule ◽  
Significant Prolongation ◽  
Inhibitory Domain

SummaryThe chimaeric molecule rscu-PA-40kDA/Hir (M23) comprises the kringle and protease domain of saruplase (rscu-PA) and a thrombin inhibitory domain fused to the C-terminus of the protease domain. The 27 amino acid long thrombin inhibitory domain contains a sequence directed to the active site of thrombin and a fragment from the C-terminal region of hirudin. 125I-radiolabelled M23 (0.03 µM) bound to thrombin that was immobilised onto CNBr-activated sepharose beads. Unlabelled M23 (0.01-10 |xM) and hirudin (0.001-10 µµM) concentra-tion-dependently displaced 125I-M23 from its binding to thrombin. Saruplase (up to 10 (iM) did not influence the thrombin binding of M23. The fibrinolytic properties of M23 and saruplase were compared in anaesthetized dogs with femoral artery and saphenous vein thrombosis. Under concomitant heparinization, the intravenous bolus injections of 1 mg/kg M23 or saruplase induced reperfusion of thrombotically occluded femoral arteries in 4 out of 5 treated animals in each case. There was one reocclusion in the M23-treated group. Time to reperfusion (23 ± 4 vs 25 ± 11 min) and maximal height of reperfusion blood flow (98 ± 21 vs 108 ± 15 % of baseline flow) did not differ significantly between the treatment groups. The time course of the lysis of incorporated 125I-fibrin radioactivity in thrombosed saphenous veins was similar after bolus injections of M23 and saruplase. The maximal dissolution of 125I-fibrin in the venous thrombosis model was 91 ± 1 % in M23-and 88 ± 5 % in saruplase-treated animals. Plasma levels of fibrinogen were not influenced and a2-antiplasmin levels were slightly reduced (-27 ± 3 %) after bolus injection of M23. In contrast, bolus injection of saruplase was accompanied by a significant decrease of fibrinogen (-55 ± 19 %) and a2-antiplasmin (-75 ±11%) plasma levels. Template bleeding times virtually did not differ before (2.8 ± 0.3 min) and 60 min after bolus injection of M23 (3.1 ± 0.3 min), whereas treatment with saruplase resulted in a significant prolongation of template bleeding time from 2.6 ± 0.2 min to 28 ± 13 min. It is concluded that the saruplase derivative M23, while inducing equieffective thrombolysis after intravenous bolus injection in dogs, causes much fewer haemostatic side effects than its parent molecule. The high thrombus-specific activity of M23 is tentatively attributed to its affinity to clot-bound thrombin.

Structuralism as a Pamphlet (On the Book by E. Reinert “How Rich CountriesGot Rich... And Why Poor Countries Stay Poor”. 2nd ed.)

2014 ◽  
pp. 147-153
Author(s):  
P. Orekhovsky
Keyword(s):  
Economic Theory ◽  
Economic Development ◽  
Structural Analysis ◽  
Increasing Returns ◽  
The Other ◽  
Static Theory ◽  
Poor Countries ◽  
Historical School ◽  
Socio Economic Development ◽  
The Relationship

The review outlines the connection between E. Reinert’s book and the tradition of structural analysis. The latter allows for the heterogeneity of industries and sectors of the economy, as well as for the effects of increasing and decreasing returns. Unlike the static theory of international trade inherited from the Ricardian analysis of comparative advantage, this approach helps identify the relationship between trade, production, income and population growth. Reinert rehabilitates the “other canon” of economic theory associated with the mercantilist tradition, F. Liszt and the German historical school, as well as a reconside ration of A. Marshall’s analysis of increasing returns. Empirical illustrations given in the book reveal clear parallels with the path of Russian socio-economic development in the last twenty years.

Sign in / Sign up

Export Citation Format

Share Document