Background: Exaggerated increases in systolic blood pressure (SBP) during exercise are associated with adverse cardiovascular events [1]. The SBP and muscle sympathetic nerve activity (MSNA) responses to mechanoreflex stimulation are exaggerated in untreated hypertensives [2]. However, it is unclear whether patients with treated-controlled vs. never treated hypertension (HTN) have different cardiovascular responses to mechanoreflex stimulation. We aimed to assess the change in SBP during the first 30 seconds of isometric handgrip (IHG) exercise. Methods: In 20 normotensive (NTN) (50±3 years, body mass index (BMI) 24±0.2 kg/m2), 9 treated-controlled HTN (56±3 years, BMI 30±0.5 kg/m2) and 7 untreated HTN (58±4 years, BMI 27±0.7 kg/m2) participants, beat-to-beat blood pressure (BP; Finapres) was measured during baseline (supine rest, 10 mins) and 30s of IHG (30% of maximal voluntary contraction). Peroneal microneurography was used to measure MSNA at baseline. Data were analysed using one-way analysis of variance (ANOVA) with Tukey test for multiple comparisons or Pearson’s correlation coefficient. Data are presented as mean ± SEM. Results: Age was similar among groups (P=0.18). BMI was higher in treated HTN (P=0.004). Office SBP was greater in untreated HTN vs treated HTN vs NTN (175±11, 139±5 vs 124±2; P<0.0001). Baseline MSNA (bursts/min) was higher in untreated HTN and treated HTN vs NTN (39±4, 38±5 vs 25±2 busts/min P=0.009). Resting HR was similar in untreated HTN, treated HTN and NTN (61±2, 64±2 vs 62±2 beats/min; P=0.28). Delta SBP and diastolic BP (DBP) during IHG was higher in combined HTN participants (SBP; 14±3 vs 6±2 mmHg; P=0.03, DBP; 7±1 vs 2±1 mmHg, P=0.005). Delta HR was not different between combined HTN vs NTN during IHG (4±1 vs 6±1 beast/min; P=0.11). Delta SBP during IHG was not different among untreated HTN, treated HTN vs NTN (10±5, 15±5 vs 6±2 mmHg; P=0.1680). However, delta DBP was higher in treated HTN vs untreated HTN and NTN (7±2, 6±1 vs 2±1 mmHg, P=0.02). Delta HR during IHG did not differ among untreated HTN, treated HTN vs NTN (6±1, 7±2 vs 4±1 beats/min; P=0.22). There was no correlation between baseline MSNA (bursts/min) and delta SBP during IHG in NTN (R=-0.17, P=0.54). In untreated HTN there was an inverse correlation of baseline MSNA (bursts/min) to delta SBP during IHG (R=-0.78, P=0.04). Conversely, treated HTN had a positive correlation of baseline MSNA (bursts/min) to delta SBP during IHG (R=0.73, P=0.04). Conclusion: The SBP response to IHG is exaggerated in HTN participants. Interestingly, untreated HTN with higher baseline MSNA had a lower SBP response to IHG, but this relationship was the opposite in treated-controlled HTN. Potentially, anti-hypertensive medication may result in re-sensitisation or upregulatation of vascular adrenergic receptors, augmenting the response to increased SNA during IHG.