Abstract
The aim of our study is to investigate the sympathetic output and baroreflex via renal sympathetic nerve activity (RSNA) recording in a model of severe hypertension which exhibits arterial, cardiac, and renal damages, the spontaneously hypertensive rat (SHR) under lowered NO bioavailability. SHR are treated from 18 to 20 weeks of age with a low dose of L-NAME, a NO synthase inhibitor, in drinking water (SHRLN) and compared to SHR and normotensive Wistar Kyoto (WKY) rats. After the two-week treatment, rats are anesthetized for RSNA, mean blood pressure (MBP), and heart rate (HR) recording. MBP is higher in SHR than in WKY and higher in SHRLN than in SHR. Compared to WKY, SHR displays an alteration in the baroreflex with a displacement of the sympathoinhibition curve to highest pressures; this displacement is greater in SHRLN rats. The bradycardic response is reduced in SHRLN compared to both SHR and WKY. In hypertensive rats, SHR and SHRLN, basal RSNA is modified, the maximal amplitude of burst is reduced, but minimal values are increased, indicating an increased basal RSNA with reduced bursting activity. The temporal correlation between RSNA and HR is preserved in SHR but altered in 10 SHRLN out of 10. The RSNA inhibition triggered by the Bezold–Jarisch reflex activation is not modified in hypertensive rats, SHR or SHRLN, in contrast to that triggered by the baroreflex. Histological analysis of the carotid bifurcation does not reveal any abnormality in SHRLN at the level of the carotid sinus. In conclusion, data indicate that the sympathetic outflow is altered in SHRLN with a strong reduction of the baroreflex sympathoinhibition and suggest that its central pathway is not involved. These additional results on SHRLN also confirm the usefulness of this model of severe hypertension with multiple target organ damages.
Highlights
Hypertension (HT) is one of the most widespread pathologies worldwide
HT is severely associated with target organ damages, i.e., the brain, heart, kidneys, arteries, and eyes as listed in Section 6 of the 2020 International Guidelines [2, 3], the sympathetic nervous system being involved at various levels [2, 3]
At 20 weeks of age, the rats are anesthetized with pentobarbital sodium (50 mg/kg i.p. as the initial dose, followed by a continuous infusion along the experiment, at 12 mg/kg/h through the penis vein). e use of pentobarbital allows to maintain blood pressure rather high and to obtain renal sympathetic nerve activity (RSNA) recordings with typical rhythms detectable, to maintain a satisfactory level of anesthesia for animal welfare, and to avoid uncontrolled movements at the level of the electrode, only leaving the respiratory movement to be managed. e trachea is cannulated, and artificial ventilation is provided with a Harvard rodent ventilator at a frequency of 70 cycles/min, with a tidal volume of 2.4–2.8 ml during surgery. e rats can breathe freely
Summary
Hypertension (HT) is one of the most widespread pathologies worldwide. A number of highly effective drug treatments exist; blood pressure control is still not satisfactory, and the prevalence remains very high. E aim of the study is to evaluate the basal sympathetic nervous system activity and baroreflex to investigate, respectively, long-term and instantaneous blood pressure control in the SHRLN model. To measure the mean sympathetic renal nerve activity (RNA), the signal is recorded in μV/s and analyzed, together with mean blood pressure (MBP) and heart rate (HR), via the data acquisition and analysis system AcqKnowledge 3.7.3 (Biopac).
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