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

Abstract

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...

Rice Bran Fractions Improve Blood Pressure, Lipid Profile, and Glucose Metabolism in Stroke-Prone Spontaneously Hypertensive Rats

“…Hypertension, a manifestation of cardiovascular disease, has continued to be a major cause of morbidity and death. Pharmacological treatment using drugs such as enalapril, losartan, and ramipril has shown that these agents have the capability to act as antihypertensive drugs ( − ). Their antihypertensive actions are due to their ability to inhibit the angiotensin-1-converting enzyme (ACE).…”