Acetylcholine and bradykinin enhance hypotension and affect the function of remodeled conduit arteries in SHR and SHR treated with nitric oxide donors.
Discrepancy was found between enhanced hypotension and attenuated relaxation of conduit arteries in response to acetylcholine (ACh) and bradykinin (BK) in nitric oxide (NO)-deficient hypertension. The question is whether a similar phenomenon occurs in spontaneously hypertensive rats (SHR) with a different pathogenesis. Wistar rats, SHR, and SHR treated with NO donors [molsidomine (50 mg/kg) or pentaerythritol tetranitrate (100 mg/kg), twice a day, by gavage] were studied. After 6 weeks of treatment systolic blood pressure (BP) was increased significantly in experimental groups. Under anesthesia, the carotid artery was cannulated for BP recording and the jugular vein for drug administration. The iliac artery was used for in vitro studies and determination of geometry. Compared to control, SHR showed a significantly enhanced (P < 0.01) hypotensive response to ACh (1 and 10 microg, 87.9 +/- 6.9 and 108.1 +/- 5.1 vs 35.9 +/- 4.7 and 64.0 +/- 3.3 mmHg), and BK (100 microg, 106.7 +/- 8.3 vs 53.3 +/- 5.2 mmHg). SHR receiving NO donors yielded similar results. In contrast, maximum relaxation of the iliac artery in response to ACh was attenuated in SHR (12.1 +/- 3.6 vs 74.2 +/- 8.6% in controls, P < 0.01). Iliac artery inner diameter also increased (680 +/- 46 vs 828 +/- 28 microm in controls, P < 0.01). Wall thickness, wall cross-section area, wall thickness/inner diameter ratio increased significantly (P < 0.01). No differences were found in this respect among SHR and SHR treated with NO donors. These findings demonstrated enhanced hypotension and attenuated relaxation of the conduit artery in response to NO activators in SHR and in SHR treated with NO donors, a response similar to that found in NO-deficient hypertension.
Gerová
M
M
Institute of Normal and Pathological Physiology, Academy of Sciences, 813 71 Bratislava, Slovakia. maria.gerova@savba.sk
Kristek
F
F
Cacányiová
S
S
Cebová
M
M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000502:physiology; D007022:Hypotension / Q000139:chemically induced / Q000378:metabolism*; D007083:Iliac Artery / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D008297:Male; D008981:Molsidomine / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000187:drug effects; D010417:Pentaerythritol Tetranitrate / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D014665:Vasodilator Agents / Q000494:pharmacology*
D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D010417:Pentaerythritol Tetranitrate; D008981:Molsidomine; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D001920:Bradykinin