1 The effects of pregnancy on mesenteric arterial function were examined in constantly perfused (5mlmin-1) mesenteric arterial beds isolated from 21-day pregnant rats. The function of sympathetic and sensory-motor perivascular nerves, endothelium and smooth muscle was examined. The role of nitric oxide and prostaglandins in vasoconstrictor function was tested by use of NG-nitro-L-arginine methyl ester (L-NAME; 100 uM) and indomethacin (10 iM), respectively.2 Electrical field stimulation (EFS; 4-32 Hz, 1 ms, 90 V, 30 s) at basal tone elicited frequency-dependent vasoconstriction which was markedly reduced in preparations from pregnant rats at all frequencies. Vasoconstrictor responses to vasopressin and endothelin were also reduced in pregnancy and there was a trend towards a reduction in maximal responses to noradrenaline (NA). In contrast, there was no difference in vasoconstrictor responses to ATP, 5-hydroxytryptamine (5-HT) or angiotensin II. 3 L-NAME (100 gM) augmented responses to EFS, NA, ATP and vasopressin in control mesenteric arterial preparations. In contrast, L-NAME augmented responses only to EFS in pregnancy, having no significant effect on responses to NA, ATP and vasopressin.4 Indomethacin (10 gM) attenuated responses to NA and vasopressin, but not to EFS, in controls and in pregnancy. Responses to ATP were attenuated by indomethacin in controls but not in pregnancy. 5 Mesenteric preparations from pregnant rats were resistant to having tone raised by continuous perfusion with methoxamine. Despite an approximately 10 fold greater concentration of methoxamine, there was a significantly smaller increase in tone in preparations from pregnant, 34.27+4.8mmHg(n= 11) compared to control, 65.92+5.4mmHg (n= 11), rats. EFS (4-12Hz, 60V, 0.1Ims, 30s) in the presence of guanethidine (5 gM) to block sympathetic neurotransmission elicited frequency-dependent vasodilatation due to activation of sensory-motor nerves. Percentage relaxations were similar in preparations from pregnant and non-pregnant rats. 6 Dose-dependent endothelium-dependent vasodilatations to acetylcholine and ATP were similar in preparations from pregnant and non-pregnant rats. Endothelium-independent vasodilatation to sodium nitroprusside and to calcitonin gene-related peptide were also similar between the two groups. 7 There was no significant difference in the basal perfusion pressure of mesenteric arterial beds from control (21.3 + 1.0 mmHg, n = 24) and pregnant (20.2 + 1.2 mmHg, n = 23) rats. However, a step-wise increase in perfusate flow from 5 to 10, 15, 20 and 24 ml min-' produced smaller increases in perfusion pressure in pregnancy compared to the controls. L-NAME (100,tM) or indomethacin (10jiM) had no significant effect on the relationship between flow and perfusion pressure. 8 The present results show that prejunctional changes are involved in blunted sympathetic vasoconstriction of rat mesenteric arteries in pregnancy. Non-specific postjunctional changes are implicated in the reduced constrictor responses to applied methoxamine, ...