Metformin, an antidiabetic agent, potentiates insulin action and reduces insulin resistance. We examined the antihypertensive effects and vascular effects of metformin in spontaneously hypertensive rats (SHR). Wistar-Kyoto normotensive (WKY) and SHR were injected with metformin (100 mg/kg) or saline subcutaneously twice daily for 4 weeks. Blood pressure was recorded by a tail-cuff plethesmographic method. Metformin treatment significantly attenuated (P < .05) the increase in blood pressure in metformin treated SHR versus untreated control SHR. At the end of the experimental period of 4 weeks, metformin-treated SHR had a mean blood pressure that was 34 mm lower than that of untreated SHR. Metformin treatment had no significant effect on blood pressure in WKY rats. Treatment of SHR aortic smooth muscle (SM) cells with metformin (2 micrograms/mL) for 24 h significantly decreased (P < .05) arginine vasopressin- and thrombin- stimulated increase in [Ca2+]i. However, metformin treatment did not have a significant effect on the basal [Ca+]i. Incubation of SHR aortic SM cells with OH-L-arginine (25 to 100 mumol/L) for 24 h increased nitrite production in a dose dependent manner. Metformin (5 micrograms/mL) treatment of SM cells increased nitrite production at all concentrations of OH-L-arginine; however, differences were significant (P < .05) only at 25 and 50 mumol/L OH-L-arginine. These results suggest that metformin may be decreasing arterial pressure in the SHR, at least in part, by attenuating the agonist-stimulated [Ca2+]i response in SHR vascular smooth muscle cells.

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and Implications A dose-dependent response of GH plasma concentration to icv injection of 3, 10 and 30 µg/kg BW of the GHsecretagogue, L-692,585 (585) was established in Yorkshire barrows (40-45 kg BW). Icv administration of CRH at 150 µg/kg BW did not raise basal GH concentration compared with saline treatment, and icv injection of 585 at three dosages did not significantly alter cortisol plasma concentration. Icv injection of SRIF dose-dependently decreased GH plasma concentration, whereas icv treatment of SRIF + 585 dosedependently increased GH concentration but at peak levels less than seen with 585 alone. Icv injection of pGAL modestly increased GH peak concentration, whereas when given in combination with 585 acutely raised GH plasma concentration. GH plasma concentration remained at basal levels after icv injection of pNPY, whereas when given in combination with 585 modestly elevated GH concentration at peak levels less than seen with 585 alone. The administration of 585 icv elicited a slower and less robust GH response than that following iv 585; desensitization of the GH response occurred following repeated icv 585 but not repeated iv 585. These findings demonstrate that 585, administered iv or icv, is a potent GH-secretagogue and confirm its central role in the pig.