The effect of renal sympathetic denervation on nocturnal dipping in patients with resistant hypertension; observational data from a tertiary referral centre in the Republic of Ireland.

OBJECTIVE: Renal sympathetic denervation (RSD) is an emerging device based treatment for patients with resistant hypertension. Nocturnal dipping (ND) is defined as a decrease in BP of 10-20 % during sleep, and has been shown to be protective against cardiovascular disease. This study examined the effect of RSD on the 24 h BP profile of patients with resistant hypertension. METHODS AND RESULTS: The first 23 consecutive patients with resistant hypertension scheduled for renal denervation in a single centre were included. 24 h ambulatory blood pressure monitors (ABPM) were given to patients pre-procedure and 9 months post-procedure. RSD led to a statistically non-significant reduction in overall 24 h ABPM BP (150/85 ± 12/9 vs. 143/84 ± 15/11 mmHg; P > 0.05) despite a reduction in the number of antihypertensive medications (4.9 ± 1.2 vs. 4.3 ± 1.2; P = 0.001). There were improvements in systolic ND 1.7 ± 8 vs. 5.2 ± 8 %; P < 0.05), diastolic ND (5.2 ± 8 vs. 10.2 ± 9 %; P < 0.05) and mean arterial pressure (MAP) ND (4.2 ± 8 vs. 8.0 ± 8 %; P < 0.05). Non-significant changes in ND status were observed in systolic (17 vs. 43 % of participants; P > 0.05), diastolic (30 vs. 43 % of participants; P > 0.05) and MAP (22 vs. 39 % of participants; P > 0.05) measurements. CONCLUSIONS: These data suggest that RSD may lead to an improvement in nocturnal dipping in selected patients with resistant hypertension. This may have cardiovascular benefits even if reduction in BP is not achieved with RSD.

The effects of N-methyl-D-aspartate agonists and antagonists on isolated bovine cerebral arteries.

This pharmacologic study examines the direct cerebrovascular effects of N-methyl-D-aspartate (NMDA) receptor agonists and antagonists to determine whether large cerebral arteries have NMDA receptors. Bovine middle cerebral arteries were cut into rings to measure isometric tension development in vitro. Two competitive agonists, L-glutamate and NMDA, each had negligible effects on ring tension in the absence of exogenous vasoconstrictors. L-glutamate (in high concentrations) produced direct relaxation of potassium (K+)-constricted arteries, but the relaxation was not selective for L-glutamate, D-glutamate, or mannitol. Relaxation with L-glutamate was abolished when it was isosmotically substituted in the K(+)-rich medium. NMDA (in the absence or presence of glycine) and two competitive antagonists, 2-amino-5-phosphopentanoic acid (AP5) and (+/-)-3-(s-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), each had little effect on the tone of arteries preconstricted with potassium or the stable thromboxane A2 analog U-46,619. Three noncompetitive antagonists (S(+)-ketamine, dizocilpine, and dextrorphan) and their steroeisomers (R(-)-ketamine, (-)MK-801, and levorphanol) each produced dose-dependent relaxation of K(+)- or U-46,619-constricted arteries; relaxation was not selective for the (+) or (-) stereoisomers. These results suggest that large cerebral arteries lack NMDA receptors mediating constriction or relaxation. All noncompetitive antagonists dilated cerebral arteries, but by mechanisms that were not stereospecific.

Ketamine directly dilates bovine cerebral arteries by acting as a calcium entry blocker.

This in vitro study was performed to determine the role of calcium in ketamine-induced cerebral vasodilation. Isolated bovine middle cerebral arteries were cut into rings to measure isometric tension development or into strips to measure radioactive 45Calcium (45Ca) uptake. Ketamine produced direct relaxation of arterial rings; the relaxation was attenuated in Ca(2+)-deficient media. Ketamine produced dose-related relaxation of arteries preconstricted with potassium, a stable thromboxane A2 analogue, or endothelin. Endothelial stripping with Triton X-100 had no effect on subsequent ketamine-induced relaxation. In Ca(2+)-deficient media containing potassium or the stable thromboxane A2 analogue, ketamine produced competitive inhibition of subsequent Ca(2+)-induced constriction. Ketamine blocked potassium- and thromboxane A2-stimulated 45Ca uptake in a dose-dependent manner, but had no effect on basal 45Ca uptake, the externally bound 45Ca content, or the volume of the 3H-sorbitol space. These results indicate that ketamine can directly dilate cerebral arteries by acting as a calcium channel antagonist; ketamine inhibits 45Ca uptake through both potential-operated (potassium) and receptor-operated (thromboxane A2) channels in cerebrovascular smooth muscle.