title: Increased renal vascular sensitivity to angiotensin II in hypertension is due to decreased response to prostaglandins.
abstract: OBJECTIVE
  An enhanced sensitivity to angiotensin II in the renal circulation has been demonstrated in the pre-hypertensive phase both in the spontaneously hypertensive rat and in man. To further characterize this abnormality and the role of prostanoids, renal haemodynamics in normotensive young men with a positive (PFH) or a negative (NFH) family history of hypertension were studied.
  
  
  METHODS
  Renal vascular reactivity was assessed during infusion of angiotensin II with and without inhibition of prostaglandin synthesis. Normotensive men with PFH (n = 13) and with NFH (n = 10) with a mean age of 38 years were given on two different occasions: (i). angiotensin II infusion i.v. (0.1, 0.5 and 1.0 ng/kg per min) and (ii). angiotensin II infusion after inhibition of prostaglandin synthesis with indomethacin (150 mg daily three consecutive days). Glomerular filtration rate (GFR) and renal plasma flow were measured with renal clearances of chromium edetic acid and para-aminohippuric acid.
  
  
  RESULTS
  Before angiotensin II challenge, the groups did not differ with respect to blood pressure, body mass index, plasma renin activity, GFR, renal blood flow (RBF) or urinary sodium excretion. There was no significant difference in systolic or diastolic blood pressure response to angiotensin II between the two groups. In PFH, the lowest angiotensin II dose caused a significant decrease in RBF and increase in renal vascular resistance (RVR) from baseline (P < 0.01 for both). In NFH, only the highest angiotensin II dose produced a significant decrease in RBF and increase in RVR (P < 0.01 for both). During inhibition of prostaglandin synthesis, all three angiotensin II doses caused a significant decrease in RBF (P < 0.02) and increase in RVR (P < 0.02) also in NFH. The renal haemodynamic difference between PFH and NFH was thus eliminated.
  
  
  CONCLUSIONS
  These findings indicate that young human subjects with a positive family history of hypertension have a defective vasodilator prostaglandin system, which is responsible for increased renal vascular sensitivity to angiotensin II. Enhanced renal vasoconstriction may be an early event leading to the generation of primary hypertension.
authors.affiliation: Department of Nephrology, Sahlgrenska University Hospital, Göteborg, Sweden.
authors.forename: Eva
authors.initials: E
authors.lastname: Palmgren
authors.forename: Bengt
authors.initials: B
authors.lastname: Widgren
authors.forename: Mattias
authors.initials: M
authors.lastname: Aurell
authors.forename: Hans
authors.initials: H
authors.lastname: Herlitz
mesh_terms: D000328:Adult; D000804:Angiotensin II / Q000008:administration & dosage* / Q000097:blood; D001794:Blood Pressure / Q000502:physiology; D015992:Body Mass Index; D002317:Cardiovascular Agents / Q000008:administration & dosage; D003971:Diastole / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D020022:Genetic Predisposition to Disease; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006339:Heart Rate / Q000502:physiology; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D007213:Indomethacin / Q000008:administration & dosage; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D011453:Prostaglandins / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects; D012083:Renin / Q000187:drug effects / Q000378:metabolism; D013223:Statistics as Topic; D013599:Systole / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000008:administration & dosage*
chemical_list: D002317:Cardiovascular Agents; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D011451:Prostaglandin-Endoperoxide Synthases; D012083:Renin; D007213:Indomethacin