Effects of 1,1-dimethylguanidine administration on blood pressure, heart rate and renal sympathetic nerve activity in normotensive and spontaneously hypertensive rats.
1,1-dimethylguanidine (DMG) is an endogenous nitric oxide (NO) synthesis inhibitor. This study investigates the effects of exogenous DMG administration, in anaesthetized spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY). Mean blood pressure (MBP), heart rate (HR) and renal sympathetic nerve activity (SNA) were recorded in 12- to 14-week old, anaesthetized SHR and WKY. Each rat received increasing bolus injections of DMG intravenously (1.03, 2.05, 6.39, 20.45 and 51.15 mg kg-1). In separate experiments, SHR received L-arginine or D-arginine in a dose of 300 mg kg-1 followed by DMG at 6.39 mg kg-1. Thirty minutes later they received the same doses of the respective arginines followed by DMG at 20.45 mg kg-1 DMG induced dose-dependant increases in MBP in SHR and WKY. In SHR, HR increased with increasing doses of DMG (except at the near-toxic doses of 51.15 mg kg-1), whereas in WKY HR decreased with increasing doses of DMG. The net change of renal SNA ranged from -5 +/- 3 to -55 +/- 12% in SHR and from -6 +/- 8 to -66 +/- 8% in WKY. Pre-treatment with L-arginine in SHR partly inhibited the pressor effect and attenuated the inhibition of renal SNA induced by DMG, but had little effect on HR. Thus the administration of NO inhibitor DMG could alter cardiovascular function and sympathetic nerve activity, and subsequently resulted in tachycardia in SHR and bradycardia in WKY.
Zhang
W
W
Department of Clinical Pharmacology, Sahlgrenska University Hospital, Gothenburg, Sweden.
Pettersson
A
A
Thorén
P
P
Hedner
T
T
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008760:Methylguanidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013564:Sympathetic Nervous System / Q000187:drug effects*
D008760:Methylguanidine; C042632:N,N-dimethylguanidine