Afferent renal nerve input is involved in blood pressure elevation through activation of angiotensin receptor type 1 in hypothalamic paraventricular nucleus in stroke‐prone spontaneously hypertensive rats
Authors: Ikeda Shota , Shinohara Keisuke , Kashihara Soichiro , Tsutsui Hiroyuki 
Published: April 2020

Background

Renal nerves contain both sympathetic efferent fibers and sensory afferent fibers. Activation of efferent renal nerves increases renin release and renal sodium reabsorption, causing hypertension. However, previous studies suggested that the contribution of afferent renal nerves to blood pressure (BP) regulation may differ among the animal models of hypertension. Activation of brain renin‐angiotensin system, specifically angiotensin receptor type 1 (AT1R), in hypothalamic paraventricular nucleus (PVN), which receives afferent renal input, is crucially involved in BP elevation. Therefore, the aim of this study was to examine whether the afferent renal input contributes to BP elevation through AT1R activation in the PVN in stroke‐prone spontaneously hypertensive rats (SHRSP).

Methods

In chronic experiment, total renal denervation (TRDN), selective afferent renal denervation (ARDN), or sham surgery was performed in male SHRSP at 10 weeks of age, which is the developing phase of hypertension. ARDN was produced by wrapping renal artery and vein with capsaicin‐soaked gauze. Systolic BP was measured by tail‐cuff method at baseline and 2 and 6 days after surgery. In acute experiment, we evaluated the effect of AT1R blockade with losartan in the PVN on pressor response to afferent renal nerve stimulation by intrapelvic infusion of 10 μM capsaicin under anesthesia in male Wistar‐Kyoto rats (WKY) and SHRSP at 10 weeks of age.

Results

Systolic BP was sequentially increased at day 2 and day 6 in sham‐operated SHRSP ([n=4], baseline, 188.3±9.2 mmHg; day 2, 192.1±8.1 mmHg; day 6, 201.1±3.9 mmHg). In both ARDN‐SHRSP and TRDN‐SHRSP, systolic BP was decreased from baseline at day 2 after surgery (ARDN [n=4], baseline, 187.3±10.3 mmHg; day 2, 170.5±5.2 mmHg; p=0.085; TRDN [n=4], baseline, 186.4±5.9 mmHg; day2 145.1±4.2 mmHg; p=0.003), and the decrease in systolic BP was smaller in ARDN‐SHRSP than in TRDN‐SHRSP (ARDN, −16.7±13.2 mmHg; TRDN, ‐ 41.4±10.0 mmHg; p=0.03). Although systolic BP was increased at day 6 compared to day 2 in ARDN‐SHRSP and TRDN‐SHRSP (ARDN, 197.8±14.9 mmHg; TRDN, 185.8±19.3 mmHg), the BP change from baseline to day 6 was smaller in ARDN‐SHRSP and TRDN‐SHRSP compared with sham‐operated SHRSP. We validated TRDN and ARDN by immunohistochemistry and western blotting: in the renal pelvis, both CGRP and tyrosine hydroxylase (a marker for afferent and efferent renal nerves, respectively) were abolished in TRDN‐SHRSP, and CGRP was selectively abolished in ARDN‐SHRSP. In acute experiment, BP elevation induced by afferent renal nerve stimulation was greater in SHRSP than in WKY (Δmean BP, SHRSP [n=4],12.2±4.1 mmHg; WKY [n=4], 6.6±5.4 mmHg; p=0.07). Prior microinjection of losartan into the PVN attenuated the pressor response to afferent renal nerve stimulation in SHRSP (Δmean BP, 1.1±4.4 mmHg, p=0.04 vs before losartan), but not in WKY (Δmean BP, 3.2±6.7 mmHg, p>0.10 vs before losartan).

Conclusion

Not only efferent renal nerve activation but afferent renal nerve input contributes to development of hypertension in SHRSP. The AT1R activation in the PVN may be involved in its mechanism.