Abstract-Pressor effects of NG-monomethyl-L-arginine (L-NMMA), a selective inhibitor of nitric oxide production from L-arginine, on mean blood pressure (MBP) were investigated in conscious Wistar Kyoto rats (WKY) and stroke-prone spon taneously hypertensive rats (SHRSP). L-NMMA (0.1-10 mg/kg, i.v.) elicited a dose-dependent increase in the MBP of WKY and SHRSP. The pressor response to L-NMMA was more marked in SHRSP than in WKY. These results suggest that nitric oxide may play an important role in the blood pressure regulation in the conscious SHRSP.
NG -Monomethyl L-arginine (L-NMMA; 0.1-10 mg/kg , i.v. ), a selec tive inhibitor of nitric oxide (NO) synthesis derived from L-arginine, elicited a greater increase in blood pressure in urethane/a-chloralose and pentobarbital-anesthetized rats than in conscious Wistar rats. The pressor response to phenylephrine was almost equivalent in both conscious and anesthetized rats. These findings suggest that the ex perimental conditions (anesthetized or conscious) modify the spontaneously released NO's contribution to blood pressure regulation in vivo.One of the endothelium-derived relaxing factors (EDRFs), first described by Furchgott and Zawadzki (1), has been identified as nitric oxide (NO) or a labile nitroso-compound (2, 3). Recent lines of evidence suggest that the guanidino nitrogen of L-arginine is the en dogenous substrate for endothelial NO syn thesis, and NG-mononethyl-L-arginine (L NMMA) competitively inhibits the generation of NO from L-arginine (4-6). NO synthesis from L-arginine is not limited to vascular en dothelium; it has also been shown to occur in vascular smooth muscle, vasodilator nerve and activated macrophages, and this is also inhib ited by L-NMMA (6-8). Thus, L-NMMA can be utilized as a tool to selectively inhibit NO production. One of us and others have pro posed that the basal and acetylcholine-induced NO production are sufficient to modulate peripheral vascular resistance; hence NO may play a role in arterial pressure homeostasis (9 -11) . In anesthetized guinea pigs (9, 12) and rabbits (10), L-NMMA, but not D-NMMA, elicits a large and sustained increase in arterial blood pressure (BP); this response is reversed by L-arginine. In conscious rats, L-NMMA also elicits an increase in BP (13). However, L-NMMA elicits a much greater BP increase in anesthetized guinea pigs (9) than in con scious rats (13). Then, we have examined if general anesthetic agents have any effect on the pressor response to L-NMMA using con scious and anesthetized rats.Twelve to 15 week-old male Wistar rats were used. A group of rats was anesthetized with urethane plus a-chloralose (500 mg/kg and 100 mg/kg, i.p., respectively) and a second group of rats was anesthetized with pentobarbital (65 mg/kg i.p.); and then both groups were subjected to the subsequent ex periments (see below). In a third group of rats, under sodium thiopental (40 mg/ kg, i.p.) anesthesia, indwelling polyethylene catheters (PE 10) were inserted into the distal aorta via the femoral artery for BP measurement and into the jugular vein for drug administration according to the methods described before (13). The catheters were filled with heparin
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