Renal Medulla and Bradykinin During the Development of Hypertension in SHR

O’Sullivan, Joseph B.; Bertram, John F.; Harrap, Stephen

doi:10.1111/j.1440-1681.1995.tb02045.x

Cited by 3 publications

(2 citation statements)

References 9 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In newborn rats chronically treated with Hoe 140 the heart to body weight ratio was significantly increased [13]. Moreover, in spontaneously hypertensive rats, 4 weeks of treatment with Hoe 140 resulted in a persistent increase in renal medullary volume [22]. In these studies the experimental conditions were not representative of the physiological regulation (i.e.…”

Section: Discussionmentioning

confidence: 94%

Chronic Bradykinin Receptor Blockade Modulates Neonatal Renal Function

1999

View full text Add to dashboard Cite

Recent data indicate that bradykinin participates in the regulation of neonatal glomerular function and also acts as a growth regulator during renal development. The aim of the present study was to investigate the involvement of bradykinin in the maturation of renal function. Bradykinin β₂-receptors of newborn rabbits were inhibited for 4 days by Hoe 140. The animals were treated with 300 μg/kg s.c. Hoe 140 (group Hoe, n = 8) or 0.9% NaCl (group control, n = 8) twice daily. Clearance studies were performed in anesthetized rabbits at the age of 8–9 days. Bradykinin receptor blockade did not impair kidney growth, as demonstrated by similar kidney weights in the two groups, nor did it influence blood pressure. Renal blood flow was higher, while renal vascular resistance and filtration fraction were lower in Hoe 140-treated rabbits. No difference in glomerular filtration rate was observed. The unexpectedly higher renal perfusion observed in group Hoe cannot be explained by the blockade of the known vasodilator and trophic effect of bradykinin. Our results indicate that in intact kallikrein-kinin system is necessary for the normal functional development of the kidney.

show abstract

Section: Discussionmentioning

confidence: 94%

Chronic Bradykinin Receptor Blockade Modulates Neonatal Renal Function

1999

View full text Add to dashboard Cite

show abstract

“…5 We have also demonstrated reduced size of the renal medulla after ACE-inhibitor treatment in young SHR, and bradykinin seemed an important factor in this phenomenon. 6 In the renal medulla, bradykinin binds to renal medullary interstitial cells (RMICs) 7 that produce renal medullary neutral lipids (RMNLs). 8 RMNLs have important effects on BP through vasodilator and sympatholytic activities.…”

mentioning

confidence: 99%

Long-Term Effects of Angiotensin-Converting Enzyme Inhibition on Renal Medullary Neutral Lipid in Spontaneously Hypertensive Rats

O’Sullivan

Harrap

1999

Hypertension

Self Cite

View full text Add to dashboard Cite

Abstract-Short-term treatment of young spontaneously hypertensive rats (SHR) with angiotensin-converting enzyme (ACE) inhibitors reduces systolic blood pressure. Renal medullary neutral lipids (RMNLs) have vasodilator properties that may explain the effects of ACE inhibition. We measured RMNL levels of SHR treated between 6 and 10 weeks of age with (1) vehicle, (2) ramipril 1 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 , (3) the bradykinin B 2 receptor antagonist icatibant 0.5 mg ⅐ kg Ϫ1 ⅐ d Ϫ1, or (4) icatibant 0.5 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 plus ramipril 1 mg ⅐ kg Ϫ1 ⅐ d Ϫ1 . RMNLs were quantified by oil red O fluorescence at 10 and 20 weeks of age. Systolic blood pressure (BP) was measured by tail-cuff plethysmography. Ramipril reduced BP at 10 weeks of age and increased RMNLs compared with controls (0.99Ϯ0.07% versus 0.56Ϯ0.06%, PϽ0.01). Icatibant alone had no significant effect on RMNLs (0.55Ϯ0.04%) but attenuated the increase in RMNLs by ramipril (0.81Ϯ0.05%). In control SHR, the increase in BP between 10 and 20 weeks of age was associated with a significant increase in RMNLs (0.79Ϯ0.09%). SHR that had received ramipril had significantly lower BP than controls at 20 weeks of age, but RMNL was not significantly different (0.92Ϯ0.10%). Therefore, in young SHR, ACE inhibition increases RMNLs and reduces blood pressure, an effect that appears to depend on bradykinin. The changes in RMNLs at the age of 10 weeks paralleled long-term BP effects and may be involved in setting the BP track in SHR. (Hypertension. 1999;33:1214-1217.) Key Words: bradykinin Ⅲ kidney medulla Ⅲ lipids Ⅲ interstitial cells A ngiotensin-converting enzyme (ACE) inhibitors decrease blood pressure (BP) and reduce cardiac and vascular hypertrophy in spontaneously hypertensive rats (SHR). 1 Brief ACE inhibitor treatment of young SHR causes persistent hypotensive effects. 1 Reduction of angiotensin II (Ang II) formation is considered central in the antihypertensive actions of ACE inhibitors. However, these effects seem to depend also on increased bradykinin levels during the treatment phase. Previous studies have demonstrated that administration of the bradykinin B 2 receptor antagonist icatibant with an ACE inhibitor prevented the long-term reduction in systolic BP found after ACE-inhibitor treatment of young SHR. 2 The kidney seems to be an important factor for the long-term effects of ACE inhibition. Transplantation studies suggest that the level of BP follows the kidney after ACEinhibitor treatment. 3 Other evidence indicates that the renal medulla may be of particular importance to BP effects of ACE inhibition. In doses that have no effect when injected intravenously, ACE inhibitor injected directly into the renal medulla of SHR increases medullary blood flow, 4 with an associated decrease in arterial pressure. Chemical renal papillectomy of young SHR during ACE-inhibitor treatment prevents long-term reduction in BP. 5 We have also demonstrated reduced size of the renal medulla after ACE-inhibitor treatment in young SHR, and bradykinin seemed an important factor in this phen...

show abstract

Pharmacology and Cardiovascular Implications of the Kinin-Kallikrein System

Dendorfer

Wolfrum

Dominiak

1999

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

Kinins are peptide hormones that can exert a significant influence on the regulation of blood pressure and vascular tone due to their vasodilatatory, natriuretic and growth modulating activity. Their cardiovascular involvement in physiological and pathophysiological situations has been studied intensively since inhibitors for angiotensin I-converting enzyme and selective receptor antagonists have become available for pharmacologically potentiating or inhibiting kinin-mediated reactions. Molecular biological analysis and the establishment of genetically modified animal models have also allowed newer information to be acquired on this subject. In this review, the components and cardiovascularly relevant mechanisms of the kinin-kallikrein system shall be described. Organ-specific effects concerning the kidneys, the vascular system, the heart and nervous tissue shall also be illustrated. On this issue, the physiological functions and pathophysiological implications of the kinin-kallikrein system should be clearly distinguished from the many, mostly endothelium-mediated protective effects which occur during ACE inhibition due to the potentiation of kinin effects. Finally, a view shall also be cast upon newly discovered targets of action, which could be exploited for therapeutically altering the kinin-kallikrein system.

show abstract

Renal Medulla and Bradykinin During the Development of Hypertension in SHR

Cited by 3 publications

References 9 publications

Chronic Bradykinin Receptor Blockade Modulates Neonatal Renal Function

Chronic Bradykinin Receptor Blockade Modulates Neonatal Renal Function

Long-Term Effects of Angiotensin-Converting Enzyme Inhibition on Renal Medullary Neutral Lipid in Spontaneously Hypertensive Rats

Pharmacology and Cardiovascular Implications of the Kinin-Kallikrein System

Contact Info

Product

Resources

About