Pressor response to pulsatile compression of the rostral ventrolateral medulla mediated by nitric oxide and c-fos expression

Abstract

It has been reported that neurovascular compression of the rostral ventrolateral medulla might be causally related to essential hypertension. Recently, we found that pulsatile compression of the rostral ventrolateral medulla increases sympathetic nerve activity and elevates arterial pressure via activation of glutamate receptors in rats. We also found that increases in sympathetic and cardiovascular activities by microinjection of L-glutamate into the rostral ventrolateral medulla are mediated by c-fos expression-related substance(s) following activation of the nitric oxide-cyclic GMP pathway. Herein, we investigated whether responses to pulsatile compression are mediated by local activation of the nitric oxide-cyclic GMP pathway and/or c-fos expression-related substance(s) in rats. Increases in arterial pressure (15+/-1 mmHg), heart rate (9+/-1 b.p.m.), and sympathetic nerve activity (% change: 8.5+/-1.1%) induced by pulsatile compression were partially but significantly inhibited after local microinjection of a nitric oxide synthase inhibitor, L-N(G)-nitroarginine methyl ester (8+/-2 mmHg, 1+/-1 b.p.m., 4.0+/-1.3%; P<0.05 vs compression without pretreatment) or 7-nitroindazole (7+/-2 mmHg, 2+/-1 b.p.m., 4.0+/-1. 5%; P<0.05), or a soluble guanylate cyclase inhibitor, methylene blue (9+/-1 mmHg, 4+/-1 b.p.m., 4.1+/-1.4%; P<0.05). In addition, increases in arterial pressure, heart rate, and sympathetic nerve activity by pulsatile compression were significantly reduced 6 h after microinjection of antisense oligodeoxynucleotide to c-fos mRNA (2+/-2 mmHg, 2+/-1 b.p.m., 1.0+/-1.0%; P<0.05 vs sense oligodeoxynucleotide). These results suggest that increases in sympathetic and cardiovascular activities induced by pulsatile compression of the rostral ventrolateral medulla are mediated, at least in part, by local activation of the nitric oxide-cyclic GMP pathway and c-fos expression-related substance(s) in rats.

Figure 1

Maximum changes in mean arterial pressure, heart rate, and sympathetic nerve activity induced by unilateral pulsatile compression of the rostral ventrolateral medulla or by unilateral compression 1 min after ipsilateral microinjection of L-N^G-nitroarginine methyl ester, D-N^G-nitroarginine methyl ester, or 7-nitroindazole into the rostral ventrolateral medulla. Maximum changes by microinjection of L-N^G-nitroarginine methyl ester or 7-nitroindazole unilaterally into the rostral ventrolateral medulla without compression are also shown as controls. n=6 for all groups, ^*P<0.05 and †P<0.01 compared to compression without pretreatment and ‡P<0.05 and ≈rcub;P<0.01 compared to compression after microinjection of D-N^G-nitroarginine methyl ester. ||P<0.01 compared to microinjection of L-N^G-nitroarginine methyl ester and ¶;P<0.01 compared to 7-nitroindazole without compression. L-NAME, L-N^G-nitroarginine methyl ester; D-NAME, D-N^G-nitroarginine methyl ester; 7-NI, 7-nitroindazole; AP, arterial pressure; HR, heart rate; SNA, sympathetic nerve activity. Bars represent mean±s.e.mean.

Figure 2

Maximum changes in mean arterial pressure, heart rate, and sympathetic nerve activity induced by unilateral pulsatile compression of the rostral ventrolateral medulla or by unilateral compression 10 min after ipsilateral microinjection of methylene blue into the rostral ventrolateral medulla. Maximum changes by microinjection of methylene blue unilaterally into the rostral ventrolateral medulla without compression are also shown as controls. n=6 for both groups, ^*P<0.05 and †P<0.01 compared to compression without pretreatment. ‡P<0.01 compared to microinjection of methylene blue without compression. AP, arterial pressure; HR, heart rate; SNA, sympathetic nerve activity. Bars represent mean±s.e.mean.

Figure 3

Changes in mean arterial pressure and heart rate after microinjection of antisense or sense oligodeoxynucleotide to c-fos mRNA or saline bilaterally into the rostral ventrolateral medulla. n=6 for all groups, ^*P<0.05 compared to microinjection of sense oligodeoxynucleotide to c-fos mRNA or saline. AP, arterial pressure; HR, heart rate; ODN, oligodeoxynucleotide. Bars represent mean±s.e.mean.

Figure 4

Maximum changes in mean arterial pressure, heart rate, and sympathetic nerve activity induced by unilateral pulsatile compression of the rostral ventrolateral medulla 15 min, 2 h, or 6 h after microinjection of antisense or sense oligodeoxynucleotide to c-fos mRNA or saline ipsilaterally into the rostral ventrolateral medulla. n=6 for all groups, ^*P<0.05 and ^**P<0.01 compared to microinjection of sense oligodeoxynucleotide to c-fos mRNA or saline. AP, arterial pressure; HR, heart rate; SNA, sympathetic nerve activity; ODN, oligodeoxynucleotide. Bars represent mean±s.e.mean.