Amplified respiratory–sympathetic coupling in the spontaneously hypertensive rat: does it contribute to hypertension?

Abstract

Sympathetic nerve activity (SNA) is elevated in established hypertension. We tested the hypothesis that SNA is elevated in neonate and juvenile spontaneously hypertensive (SH) rats prior to the development of hypertension, and that this may be due to augmented respiratory-sympathetic coupling. Using the working heart-brainstem preparation, perfusion pressure, phrenic nerve activity and thoracic (T8) SNA were recorded in male SH rats and normotensive Wistar-Kyoto (WKY) rats at three ages: neonates (postnatal day 9-16), 3 weeks old and 5 weeks old. Perfusion pressure was higher in SH rats at all ages reflecting higher vascular resistance. The amplitude of respiratory-related bursts of SNA was greater in SH rats at all ages (P < 0.05). This was reflected in larger Traube-Hering pressure waves in SH rats (1.4 +/- 0.8 versus 9.8 +/- 1.5 mmHg WKY versus SH rat, 5 weeks old, n = 5 per group, P < 0.01). Recovery from hypocapnic-induced apnoea and reinstatement of Traube-Hering waves produced a significantly greater increase in perfusion pressure in SH rats (P < 0.05). Differences in respiratory-sympathetic coupling in the SH rat were not secondary to changes in central or peripheral chemoreflex sensitivity, nor were they related to altered arterial baroreflex function. We have shown that increased SNA is already present in SH rats in early postnatal life as revealed by augmented respiratory modulation of SNA. This is reflected in an increased magnitude of Traube-Hering waves resulting in elevated perfusion pressure in the SH rat. We suggest that the amplified respiratory-related bursts of SNA seen in the neonate and juvenile SH rat may be causal in the development of their hypertension.

The sympathetic nervous system and blood pressure in humans: implications for hypertension

“…89 Intriguingly, the results of several studies indicate that device-guided, home-based training with slow, deep breathing can effectively reduce blood pressure in patients with hypertension, [90][91][92] although this has not been a universal finding. 93 These findings are particularly intriguing given the recent identification of an amplified bursting of SNA related to the respiratory cycle that appears to contribute to the progression and maintenance of hypertension in rats, 7 and the alterations in respiratory-sympathetic coupling recently reported in human hypertension. 39,40 Further studies are required to determine whether central sympathetic outflow is decreased by stress reduction programs, which effectively reduce blood pressure.…”

“…31,32 As in hypertensive patients, studies of the adult spontaneously hypertensive rat (SHR) have also identified a reduced cardiac parasympathetic nerve activity, 33 elevated SNA and increased noradrenaline release. 34,35 Notably, neonatal sympathectomy prevents the SHR from developing hypertension, 36 while our group, 7 and others, 37 have shown that SNA is elevated in young SHR prior to the development of hypertension. An amplified burst pattern of SNA that is respiratory related and contributes to the elevations in vascular resistance and blood pressure has also been identified in rat models of hypertension 7,38 while our preliminary investigations suggest alterations in respiratory-sympathetic coupling in human hypertension.…”

“…34,35 Notably, neonatal sympathectomy prevents the SHR from developing hypertension, 36 while our group, 7 and others, 37 have shown that SNA is elevated in young SHR prior to the development of hypertension. An amplified burst pattern of SNA that is respiratory related and contributes to the elevations in vascular resistance and blood pressure has also been identified in rat models of hypertension 7,38 while our preliminary investigations suggest alterations in respiratory-sympathetic coupling in human hypertension. 39,40 The functional implications of this remain to be verified.…”

“…Evidence from studies in both patients and animal models of hypertension strongly implicate the chronic sympathetic neural activation in the aetiology and progression of hypertension (Figure 1). 2,[6][7][8][9] The use of regional surgical sympathectomy to treat hypertension over 50 years ago before the availability of antihypertensive medications that lower sympathetic activity provides an early indication of the clinical appreciation for a significant neurogenic component to hypertension.…”

“…Evidence from studies in both patients and animal models of hypertension strongly implicate the chronic sympathetic neural activation in the aetiology and progression of hypertension ( Figure 1). 2,[6][7][8][9] The use of regional surgical sympathectomy to treat hypertension over 50 years ago before the availability of antihypertensive medications that lower sympathetic activity provides an early indication of the clinical appreciation for a significant neurogenic component to hypertension. 10 Recent clinical interventions showing impressive blood pressure lowering effects by targeting reductions in SNA [11][12][13][14] and progress in the elucidation of the central sympathetic regulatory pathways altered in hypertension [15][16][17] are part of a renaissance of interest in the control of the sympathetic nervous system and its utility as a clinical target.…”