title: Differential regulation of kallikrein, kininogen, and kallikrein-binding protein in arterial hypertensive rats.
abstract: This study was designed to determine whether the kallikrein-kinin system exerts a protective action in hypertension induced by chronic inhibition of nitric oxide synthase. N omega-nitro-L-arginine methyl ester (L-NAME, 40 mg/100 ml water) was given orally to Sprague-Dawley rats, while controls received regular tap water. Hepatic kininogen mRNA levels in the L-NAME-treated group were 2.9- and 2.5-fold higher at 3 and 4 wk, respectively, compared with control rats, whereas kallikrein-binding protein (KBP) mRNA levels were 82% and 45% of the values found in control rats at 3 and 4 wk, respectively. There was no significant change in hepatic alpha 1-antitrypsin mRNA levels under the same conditions. At 3 and 4 wk post L-NAME treatment, renal kallikrein mRNA levels were 2.5- and 3.4-fold higher than in controls, whereas renal beta-actin mRNA levels were similar between groups. Changes in the transcript levels of renal kallikrein, kininogen, and KBP were consistent with their protein levels. Immunoreactive total kininogen and low-Mr kininogen levels in sera and tissue kallikrein levels in kidney were significantly higher in the L-NAME-treated group, whereas KBP levels in the circulation were lower compared with controls. Systolic blood pressure was increased by 58 +/- 4 mmHg after 4 wk of L-NAME treatment. This effect was enhanced in rats given L-NAME in combination with HOE-140, a bradykinin B2-receptor antagonist, at the dose of 100 micrograms/day ip (79 +/- 5 vs. 58 +/- 4 mmHg, P < 0.05). This difference was confirmed by direct measurement of mean blood pressure (MBP). An intra-arterial bolus injection of 200 ng bradykinin significantly decreased MBP of L-NAME-treated rats, and this effect was blunted in the group treated with the bradykinin antagonist (-29 +/- 3 vs. -9 +/- 2 mmHg, P < 0.01). These results suggest that enhanced kallikrein and kininogen synthesis may have a protective role against the cardiovascular effects induced by chronic inhibition of nitric oxide synthesis.
authors: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston 29425, USA.
authors: C
authors: C
authors: Chao
authors: P
authors: P
authors: Madeddu
authors: C
authors: C
authors: Wang
authors: Y
authors: Y
authors: Liang
authors: L
authors: L
authors: Chao
authors: J
authors: J
authors: Chao
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D037263:Asialoglycoprotein Receptor; D065168:Bradykinin Receptor Antagonists; D002319:Cardiovascular System / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006973:Hypertension / Q000378:metabolism*; D007610:Kallikreins / Q000235:genetics / Q000378:metabolism*; D007704:Kininogens / Q000235:genetics / Q000378:metabolism*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*
chemical_list: D037263:Asialoglycoprotein Receptor; D065168:Bradykinin Receptor Antagonists; D007704:Kininogens; D011956:Receptors, Cell Surface; D001120:Arginine; D019001:Nitric Oxide Synthase; D007610:Kallikreins; D019331:NG-Nitroarginine Methyl Ester