Long-term effects of angiotensin-converting enzyme inhibition on renal medullary neutral lipid in spontaneously hypertensive rats.
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. kg-1. d-1, (3) the bradykinin B2 receptor antagonist icatibant 0.5 mg. kg-1. d-1, or (4) icatibant 0.5 mg. kg-1. d-1 plus ramipril 1 mg. kg-1. d-1. 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 (0.99+/-0.07% versus 0.56+/-0. 06%, P<0.01). Icatibant alone had no significant effect on RMNLs (0.55+/-0.04%) but attenuated the increase in RMNLs by ramipril (0. 81+/-0.05%). In control SHR, the increase in BP between 10 and 20 weeks of age was associated with a significant increase in RMNLs (0.79+/-0.09%). SHR that had received ramipril had significantly lower BP than controls at 20 weeks of age, but RMNL was not significantly different (0.92+/-0.10%). 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.
O'Sullivan
J B
JB
Department of Physiology, University of Melbourne, Parkville, Victoria, Australia.
Harrap
S B
SB
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D004396:Coloring Agents; D003627:Data Interpretation, Statistical; D006973:Hypertension / Q000503:physiopathology*; D007679:Kidney Medulla / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D050356:Lipid Metabolism; D008055:Lipids / Q000032:analysis; D018613:Microscopy, Confocal; D017257:Ramipril / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D065168:Bradykinin Receptor Antagonists; D004396:Coloring Agents; D008055:Lipids; C065679:icatibant; D017257:Ramipril; D001920:Bradykinin